Midterm 1 Reviwers 2024-09-09 02_47_24.pdf

GENERAL BIOLOGY 1 Cell Theory There are 3 tenets to the cell theory. “Tenet” means rule, idea, or principle. They are: 1. All living things are made up of one or more cells. 2. The cell is the basic unit of structure and organization in organisms. 3. Cells arise from pre-existing cells. Cell Parts...

GENERAL BIOLOGY 1 Cell Theory There are 3 tenets to the cell theory. “Tenet” means rule, idea, or principle. They are: 1. All living things are made up of one or more cells. 2. The cell is the basic unit of structure and organization in organisms. 3. Cells arise from pre-existing cells. Cell Parts and Functions 1. Cell membrane - The cell membrane supports and protects the cell. It controls the movement of substances in and out of the cells. It separates the cell from the external environment. The cell membrane is present in all the cells. - The cell membrane is the outer covering of a cell within which all other organelles, such as the cytoplasm and nucleus, are enclosed. It is also referred to as the plasma membrane. 2. Cell Wall - The cell wall is present exclusively in plant cells. It protects the plasma membrane and other cellular components. The cell wall is also the outermost layer of plant cells. - It provides shape and support to the cells and protects them from mechanical shocks and injuries. 3. Cytoplasm - The cytoplasm is a thick, clear, jelly-like substance present inside the cell membrane. - The cell organelles such as endoplasmic reticulum, vacuoles, mitochondria, ribosomes, are suspended in this cytoplasm. 4. Nucleus - The nucleus contains the hereditary material of the cell, the DNA. - It sends signals to the cells to grow, mature, divide and die. - The nucleus is surrounded by the nuclear envelope that separates the DNA from the rest of the cell. - The nucleus protects the DNA and is an integral component of a plant’s cell structure. 5. Nucleolus - The nucleolus is the site of ribosome synthesis. Also, it is involved in controlling cellular activities and cellular reproduction 6. Nuclear membrane - The nuclear membrane protects the nucleus by forming a boundary between the nucleus and other cell organelles. 7. Chromosomes - Chromosomes play a crucial role in determining the sex of an individual. Each human cells contain 23 pairs of chromosomes 8. Endoplasmic reticulum - The endoplasmic reticulum is involved in the transportation of substances throughout the cell. It plays a primary role in the metabolism of carbohydrates, synthesis of lipids, steroids and proteins. 9. Golgi Bodies - Golgi bodies are called the cell’s post office as it is involved in the transportation of materials within the cell 10. Ribosome - Ribosomes are the protein synthesizer of the cell 11. Mitochondria - The mitochondrion is called “the powerhouse of the cell.” It is called so because it produces ATP – the cell’s energy currency  12. Lysosomes - Lysosomes protect the cell by engulfing the foreign bodies entering the cell and help in cell renewal. Therefore, it is known as the cell’s suicide bags 13. Peroxisomes - Peroxisomes contain enzymes that oxidize certain molecules normally found in the cell, notably fatty acids and amino acids. Those oxidation reactions produce hydrogen peroxide, which is potentially toxic to the cell, because it has the ability to react with many other molecules. 14. Chloroplast - Chloroplasts are the primary organelles for photosynthesis. It contains the pigment chlorophyll. 15. Vacuoles - Vacuoles stores food, water, and other waste materials in the cell. For Plants 16. Cell wall - Outermost layer of plant cell, protects plasma membrane - Provides shape and support to cell, and protect from shocks 17. Chloroplast - Primary organelle for photosynthesis - Contain pigment called chlorophyll 18. Vacuoles - Stores food, water and other waste materials Both animal and plant 1. Mitochondria 2. Vacuoles 3. Cell membrane Cell Theory 1. Robert Hooke - Fist to used the term “cell” - 1665: describe chambers within cork that he observed under the microscope he made - This cork resembled “honey-comb”. He noted: cavern, bubble, or cell - At that time, he was not aware that the cork cell were dead 2. Matthias Schleiden - German botanist who said that plant tissues are composed of cells (1838) - He believed that cells were formed through crystallization 3. Theodor Schwann - German physiologist who observed that animal tissue are made out of cells in 1839 - After conversation with Schleiden, he realized that animal and plant do have similarities 4. Robert Remark - Published convincing evidence that cells are derived from other cells, but questioned by scientific communities (1852)  5. Rudolf Virchow - Published Cellular Pathology in 1855. Which has the sayings “omnis cellula a cellula”, that means all cells arise from cells - Some controversy says that Remark should be credit by Virchow because that idea is mainly from Remark 3 Postulates Energy flow (metabolism and 1. All cell is the basic unit of life; biochemistry) occurs within cells 2. All living organisms are composed of All cells are essentially the same in cells; and chemical composition 3. New cells are created from Cells carry genetic material passed to pre-existing cells. daughter cells during cellular division Eukaryote vs. Prokaryote Cells fall into one of two broad categories: prokaryotic and eukaryotic. The single-celled organisms of the domains Bacteria and Archaea are classified as prokaryotes (pro = before; karyon– = nucleus). Animal cells, plant cells, fungi, and protists are eukaryotes (eu = true). Components of Prokaryotic Cells All cells share four common components: (1) a plasma membrane, an outer covering that separates the cell’s interior from its surrounding environment; (2) cytoplasm, consisting of a jelly-like region within the cell in which other cellular components are found; (3) DNA, the genetic material of the cell; and (4) ribosomes, particles that synthesize proteins. However, prokaryotes differ from eukaryotic cells in several ways. A prokaryotic cell is a simple, single-celled (unicellular) organism that lacks a nucleus, or any other membrane-bound organelle. We will shortly come to see that this is significantly different in eukaryotes. Prokaryotic DNA is found in the central part of the cell: a darkened region called the nucleoid (Figure 1). Unlike Archaea and eukaryotes, bacteria have a cell wall made of peptidoglycan, comprised of sugars and amino acids, and many have a polysaccharide capsule (Figure 1). The cell wall acts as an extra layer of protection, helps the cell maintain its shape, and prevents dehydration. The capsule enables the cell to attach to surfaces in its environment. Some prokaryotes have flagella, pili, or fimbriae. Flagella are used for locomotion, while most pili are used to exchange genetic material during a type of reproduction called conjugation. Eukaryotic Cells In nature, the relationship between form and function is apparent at all levels, including the level of the cell, and this will become clear as we explore eukaryotic cells. The principle “form follows function” is found in many contexts. It means that, in general, one can deduce the function of a structure by looking at its form, because the two are matched. For example, birds and fish have streamlined bodies that allow them to move quickly through the medium in which they live, be it air or water. A eukaryotic cell is a cell that has a membrane-bound nucleus and other membrane-bound compartments or sacs, called organelles, which have specialized functions. The word eukaryotic means “true kernel” or “true nucleus,” alluding to the presence of the membrane-bound nucleus in these cells. The word “organelle” means “little organ,” and, as we learned earlier, organelles have specialized cellular functions, just as the organs of your body have specialized functions. Cell Size At 0.1–5.0 µm in diameter, prokaryotic cells are significantly smaller than eukaryotic cells, which have diameters ranging from 10–100 µm (Figure 2). The small size of prokaryotes allows ions and organic molecules that enter them to quickly spread to other parts of the cell. Similarly, any wastes produced within a prokaryotic cell can quickly move out. However, larger eukaryotic cells have evolved different structural adaptations to enhance cellular transport. Indeed, the large size of these cells would not be possible without these adaptations. In general, cell size is limited because volume increases much more quickly than does cell surface area. As a cell becomes larger, it becomes more and more difficult for the cell to acquire sufficient materials to support the processes inside the cell, because the relative size of the surface area across which materials must be transported declines. Cell Cycle and Cell Division A cell cycle is a series of events that takes place in a cell as it grows and divides. A cell spends most of its time in what is called interphase, and during this time it grows, replicates its chromosomes, and prepares for cell division. The cell then leaves interphase, undergoes mitosis, and completes its division. The resulting cells, known as daughter cells, each enter their own interphase and begin a new round of the cell cycle. The diagram below represents the cell cycle of an eukaryotic cell. As you can see, the eukaryotic cell cycle has several phases. The mitotic phase (M) actually includes both mitosis and cytokinesis. This is when the nucleus and then the cytoplasm divide. The other three phases (G1, S, and G2) are generally grouped together as interphase. During interphase, the cell grows, performs routine life processes, and prepares to divide. These phases are discussed below. Interphase: The Interphase of the eukaryotic cell cycle can be subdivided into the following three phases. Growth Phase 1 (G1): The cell spends most of its life in the first gap (sometimes referred to as growth) phase, G1. During this phase, a cell undergoes rapid growth and the cell performs its routine functions. During this phase, the biosynthetic and metabolic activities of the cell occur at a high rate. The synthesis of amino acids and hundreds of thousands or millions of proteins that are required by the cell occurs during this phase. Proteins produced include those needed for DNA replication. If a cell is not dividing, the cell enters the G0 phase from this phase. G0 Phase: The G0 phase is a resting phase where the cell has left the cycle and has stopped dividing. Non-dividing cells in multicellular eukaryotic organisms enter G0 from G1. These cells may remain in G0 for long periods of time, even indefinitely, such as with neurons. Cells that are completely differentiated may also enter G0. Some cells stop dividing when issues of sustainability or viability of their daughter cells arise, such as with DNA damage or degradation, a process called cellular senescence. Cellular senescence occurs when normal diploid cells lose the ability to divide, normally after about 50 cell divisions. Synthesis Phase (S): Dividing cells enter the Synthesis (S) phase from G1. For two genetically identical daughter cells to be formed, the cell’s DNA must be copied through DNA replication. When the DNA is replicated, both strands of the double helix are used as templates to produce two new complementary strands. These new strands then hydrogen bond to the template strands and two double helices form. During this phase, the amount of DNA in the cell has effectively doubled, though the cell remains in a diploid state. Growth Phase 2 (G2): The second gap (growth) (G2) phase is a shortened growth period in which many organelles are reproduced or manufactured. Parts necessary for mitosis and cell division are made during G2, including microtubules used in the mitotic spindle. Cell Division Cell division is the basis for all forms of organismal reproduction. Single-celled organisms divide to reproduce. Cell division in multicellular organisms produces specialized reproductive cells, such as egg and sperm, and is also responsible for the development of a many-celled organism from a single fertilized egg cell. In order for a cell to divide, the genome must also divide, so, in all types of cell division in all organisms, DNA replication precedes cell division. MITOSIS Mitosis is a form of eukaryotic cell division that produces two daughter cells with the same genetic component as the parent cell. Chromosomes replicated during the S phase are divided in such a way as to ensure that each daughter cell receives a copy of every chromosome. In actively dividing animal cells, the whole process takes about one hour. STAGES OF MITOSIS 1. Prophase Prophase occupies over half of mitosis. The nuclear membrane breaks down to form a number of small vesicles and the nucleolus disintegrates. A structure known as the centrosome duplicates itself to form two daughter centrosomes that migrate to opposite ends of the cell. The centrosomes organise the production of microtubules that form the spindle fibres that constitute the mitotic spindle. The chromosomes condense into compact structures. Each replicated chromosome can now be seen to consist of two identical chromatids (or sister chromatids) held together by a structure known as the centromere. 2. Prometaphase The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid-line of the cell - at right-angles to the axis formed by the centrosomes. This region of the mitotic spindle is known as the metaphase plate. The spindle fibres bind to a structure associated with the centromere of each chromosome called a kinetochore. Individual spindle fibres bind to a kinetochore structure on each side of the centromere. The chromosomes continue to condense. 3. Metaphase The chromosomes align themselves along the metaphase plate of the spindle apparatus.  4. Anaphase The shortest stage of mitosis. The centromeres divide, and the sister chromatids of each chromosome are pulled apart - or 'disjoin' - and move to the opposite ends of the cell, pulled by spindle fibres attached to the kinetochore regions. The separated sister chromatids are now referred to as daughter chromosomes. (It is the alignment and separation in metaphase and anaphase that is important in ensuring that each daughter cell receives a copy of every chromosome.) 5. Telophase The final stage of mitosis, and a reversal of many of the processes observed during prophase. The nuclear membrane reforms around the chromosomes grouped at either pole of the cell, the chromosomes uncoil and become diffuse, and the spindle fibres disappear. 6. Cytokinesis The final cellular division to form two new cells. In plants a cell plate forms along the line of the metaphase plate; in animals there is a constriction of the cytoplasm. The cell then enters interphase - the interval between mitotic divisions. MEIOSIS Meiosis is the form of eukaryotic cell division that produces haploid sex cells or gametes (which contain a single copy of each chromosome) from diploid cells (which contain two copies of each chromosome). The process takes the form of one DNA replication followed by two successive nuclear and cellular divisions (Meiosis I and Meiosis II). As in mitosis, meiosis is preceded by a process of DNA replication that converts each chromosome into two sister chromatids. Meiosis I: Separates the pairs of homologous chromosomes. In Meiosis I a special cell division reduces the cell from diploid to haploid. Prophase I: The homologous chromosomes pair and exchange DNA to form recombinant chromosomes. Prophase I is divided into five phases:  Leptotene: chromosomes start to condense. Zygotene: homologous chromosomes become closely associated (synapsis) to form pairs of chromosomes (bivalents) consisting of four chromatids (tetrads). Pachytene: crossing over between pairs of homologous chromosomes to form chiasmata (sing. chiasma). Diplotene: homologous chromosomes start to separate but remain attached by chiasmata. Diakinesis: homologous chromosomes continue to separate, and chiasmata move to the ends of the chromosomes. Prometaphase I: Spindle apparatus formed, and chromosomes attached to spindle fibres by kinetochores. Metaphase I: Homologous pairs of chromosomes (bivalents) arranged as a double row along the metaphase plate. The arrangement of the paired chromosomes with respect to the poles of the spindle apparatus is random along the metaphase plate. (This is a source of genetic variation through random assortment, as the paternal and maternal chromosomes in a homologous pair are similar but not identical. The number of possible arrangements is 2n, where n is the number of chromosomes in a haploid set. Human beings have 23 different chromosomes, so the number of possible combinations is 223, which is over 8 million.) Anaphase I: The homologous chromosomes in each bivalent are separated and move to the opposite poles of the cell Telophase I: The chromosomes become diffuse and the nuclear membrane reforms. Cytokinesis: The final cellular division to form two new cells, followed by Meiosis II. Meiosis I is a reduction division: the original diploid cell had two copies of each chromosome; the newly formed haploid cells have one copy of each chromosome.  Meiosis II: Separate each chromosome into two chromatids. The events of Meiosis II are analogous to those of a mitotic division, although the number of chromosomes involved has been halved. Meiosis generates genetic diversity through: the exchange of genetic material between homologous chromosomes during Meiosis I the random alignment of maternal and paternal chromosomes in Meiosis I the random alignment of the sister chromatids at Meiosis II Simple Diffusion Diffusion is the movement of particles down their gradient. A gradient is any imbalance in concentration, and moving down a gradient just means that the particle is trying to be evenly distributed everywhere, like dropping food coloring in water. This is what happened when we made our granola - a bunch of separate ingredients came together and spread out across the whole mixture. We call this evening-out moving “downhill”, and it doesn’t require energy. The molecule most likely to be involved in simple diffusion is water - it can easily pass through cell membranes. When water undergoes simple diffusion, it is known as osmosis. Simple diffusion is pretty much exactly what it sounds like – molecules move down their gradients through the membrane. Molecules that practice simple diffusion must be small and nonpolar*, in order to pass through the membrane. Simple diffusion can be disrupted if the diffusion distance is increased. If the alveoli in our lungs fill with fluid (pulmonary edema), the distance the gasses must travel increases, and their transport decreases. FACILITATED DIFFUSION Facilitated diffusion, not to be confused with simple diffusion, is a form of passive transport mediated by transport proteins imbedded within the cellular membrane. Facilitated diffusion allows the passage of lipophobic molecules through the cell membrane’s lipid bilayer. Just as in passive transport, molecules, particles, and ions travel freely across the cellular membrane from high concentration to low concentration in an attempt to achieve equilibrium and thereby increase the entropy of the system. Also like passive transport, the Gibbs free energy of the system is negative, allowing the particle movement to be spontaneous. Facilitated diffusion, however, uses channel proteins to facilitate solute movement. Facilitated Diffusion via channel protein across a membrane Facilitated diffusion is diffusion that is helped along (facilitated by) a membrane transport channel. These channels are glycoproteins (proteins with carbohydrates attached) that allow molecules to pass through the membrane. These channels are almost always specific for either a certain molecule or a certain type of molecule (i.e. an ion channel), and so they are tightly linked to certain physiologic functions. For example, one such transporter channel, GLUT4, is incredibly important in diabetes. GLUT4 is a glucose transporter found in fat and skeletal muscle. Insulin triggers GLUT4 to insert into the membranes of these cells so that glucose can be taken in from the blood. Since this is a passive mechanism, the amount of sugar entering our cells is proportional to how much sugar we consume, up to the point that all our channels are being used (saturation). In type II diabetes mellitus, cells do not respond as well to the presence of insulin, and so do not insert GLUT4 into their membranes. This can lead to soaring blood glucose levels which can cause heart disease, stroke, and kidney failure. Channel Proteins Channel proteins are pores immersed in the lipid bilayer membrane and are the hallmark of facilitated diffusion. All channel proteins have two things in common: They facilitate a thermodynamically favorable net movement of particles They demonstrate an affinity and specificity for the particle being transported. Channel proteins can be physically or chemically modulated through a number of different mechanisms. Voltage gating Voltage gated channel proteins are activated by a change in the electrical potential of the cellular membrane in its vicinity. When a potential difference occurs across the cellular membrane, its electromagnetic field causes a conformational change in the channel protein, allowing it to open. Ligand gating Ligand gated channel proteins are activated in response to the binding of a ligand. Typically, ligand binding occurs at an allosteric binding site independent of the channel protein’s pore. The binding of a ligand at the allosteric binding site causes a conformational change in the structure of the channel protein, subsequently causing an influx or efflux of ions. Release of the ligand allows the channel protein to return to its original shape. Structurally, ligand gated channel proteins generally differ from other channels due to the presence of an additional protein domain that serves as the allosteric binding site. Other gating Channel proteins may be gated in less common instances by methods such as light activation, mechanical activation, or secondary messenger activation. Light activated protein channels contain a photo switch through which a photon causes a conformational change in the channel protein causing it to open or close. Only one such protein channel exists naturally. Mechanically activated protein channels open or close in response to a mechanical stimulus and are vital to the touch, hearing, and balance sensations in human. Ligand-gated protein channels are typically linked to second messenger gating. Second messenger gating functions stepwise in that a neurotransmitter binds to a channel protein receptor which, in turn, reveals an active site to which the conformation-changing ligand binds. ACTIVE TRANSPORT Active transport, simply put, is the movement of particles through a transport protein from low concentration to high concentration at the expense of metabolic energy. The most common energy source used by cells is adenosine triphosphate or ATP, though other sources such as light energy or the energy stored in an electrochemical gradient are also utilized. In the case of ATP, energy is chemically harvested through hydrolysis. ATP hydrolysis in turn causes a conformational change in the transport protein which allows mechanical movement of the particle in question. Active transport systems are, therefore, energy-coupling devices as chemical and mechanical processes are linked to achieve particle movement. Active transport is classified as either Primary Active Transport or Secondary Active Transport. A ribbon structure of a commonly depicted ABC Vitamin B12 importer active transport protein. Primary Active Transport Primary active transport uses the energy found in ATP, photons, and electrochemical gradients directly in the transport of molecules from low concentration to high concentration across the cellular membrane. Using ATP The enzyme-catalyzed hydrolysis reaction removing a phosphate from ATP, thereby forming ADP, causes a conformational change in the transport protein allowing particles to influx or efflux. Enzymes catalyzing ATP-driven primary active transport are called ATPases. The most universal example of ATP hydrolysis driving primary active transport in cells is the sodium-potassium pump. The sodium-potassium pump is responsible for controlling both sodium and potassium concentrations inside the cell. The sodium-potassium pump is extremely important in maintaining the cell’s resting potential. Using Electrochemical Gradient Energy An electrochemical gradient has two components: 1) An electrical component caused by charge difference on either side of the cellular membrane 2) A chemical component resulting from differing concentrations of ions across the cellular membrane. The electrochemical gradient is generated by the presence of a proton (H+) gradient. A proton gradient is an interconvertible form of energy that can ultimately be used by the transport protein to move particles across the cellular membrane. A quintessential example of electrochemical gradient energy in primary active transport is the mitochondrial electron transport chain (ETC). The ETC uses the energy produced from the reduction of NADH to NAD+ to create a proton gradient by pumping protons into the inner mitochondrial space. Using Photon Energy The energy stored in a photon, the basic unit of light, is used to generate a proton gradient through a process similar to that found in electrochemical gradients. The stepwise passing of electrons in an electron transport chain reduces a molecule like NADH and ultimately generates a proton gradient. Plant photosynthesis is an example of primary active transport using photon energy. Chlorophyll absorbs a photon of light and consequently loses an electron which it passes pheophytin causing a subsequent electron transport chain. This ETC ultimately ends in the reduction of NADH to NAD+ creating a proton gradient across the chloroplast membrane. Secondary Active Transport Secondary active transport achieves an identical result as primary active transport in that particles are moved from low concentration to high concentration at the expense of energy. Secondary active transport, however, functions independent of direct ATP coupling. Rather, the electrochemical energy generated from pumping ions out of the cell is used. Secondary active transport is classified as either symporter of antiporter. Symports Symport secondary active transport uses a downhill movement of one particle to transport another particle against its concentration gradient. Symports move both particles in the same direction through a transmembrane transport protein. A common symport example is SGLT1, a glucose symport. SGLT1 tranports one glucose molecule into the cell for every two sodium ions transported into the cell. The SGLT1 symport is located throughout the body, particularly in the nephron of the kidney. Antiports Antiport secondary active transport moves two or more different particles across the cellular membrane in opposite directions. Antiport secondary active transport moves one particle down its concentration gradient and uses the energy generated from that process to move another particle up its concentration gradient. The sodium-calcium exchanger found throughout humans in excitable cells is a simple and common example of an antiport. Three sodium ions travel down their concentration gradient in exchange for one calcium ion. BULK TRANSPORT Cells need bulk transport mechanisms, in which large particles (or large quantities of smaller particles) are moved across the cell membrane. These mechanisms involve enclosing the substances to be transported in their own small globes of membrane, which can then bud from or fuse with the membrane to move the substance across. For instance, a macrophage engulfs its pathogen dinner by extending membrane "arms" around it and enclosing it in a sphere of membrane called a food vacuole (where it is later digested). Macrophages provide a dramatic example of bulk transport, and the majority of cells in your body don’t engulf whole microorganisms. However, most cells do have bulk transport mechanisms of some kind. These mechanisms allow cells to obtain nutrients from the environment, selectively “grab” certain particles out of the extracellular fluid, or release signaling molecules to communicate with neighbors. Like the active transport processes that move ions and small molecules via carrier proteins, bulk transport is an energy-requiring (and, in fact, energy-intensive) process. Here, we’ll look at the different modes of bulk transport: phagocytosis, pinocytosis, receptor-mediated endocytosis, and exocytosis. ENDOCYTOSIS Endocytosis (endo = internal, cytosis = transport mechanism) is a general term for the various types of active transport that move particles into a cell by enclosing them in a vesicle made out of plasma membrane. There are variations of endocytosis, but all follow the same basic process. First, the plasma membrane of the cell invaginates (folds inward), forming a pocket around the target particle or particles. The pocket then pinches off with the help of specialized proteins, leaving the particle trapped in a newly created vesicle or vacuole inside the cell. Endocytosis can be further subdivided into the following categories: phagocytosis, pinocytosis, and receptor-mediated endocytosis. Phagocytosis Phagocytosis (literally, “cell eating”) is a form of endocytosis in which large particles, such as cells or cellular debris, are transported into the cell. We’ve already seen one example of phagocytosis, because this is the type of endocytosis used by the macrophage in the article opener to engulf a pathogen. Pinocytosis Pinocytosis (literally, “cell drinking”) is a form of endocytosis in which a cell takes in small amounts of extracellular fluid. Pinocytosis occurs in many cell types and takes place continuously, with the cell sampling and re-sampling the surrounding fluid to get whatever nutrients and other molecules happen to be present. Pinocytosed material is held in small vesicles, much smaller than the large food vacuole produced by phagocytosis. Receptor-mediated endocytosis Receptor-mediated endocytosis is a form of endocytosis in which receptor proteins on the cell surface are used to capture a specific target molecule. The receptors, which are transmembrane proteins, cluster in regions of the plasma membrane known as coated pits. This name comes from a layer of proteins, called coat proteins, that are found on the cytoplasmic side of the pit. Clathrin, shown in the diagram above, is the best-studied coat protein When the receptors bind to their specific target molecule, endocytosis is triggered, and the receptors and their attached molecules are taken into the cell in a vesicle. The coat proteins participate in this process by giving the vesicle its rounded shape and helping it bud off from the membrane. Receptor-mediated endocytosis allows cells to take up large amounts of molecules that are relatively rare (present in low concentrations) in the extracellular fluid.  Although receptor-mediated endocytosis is intended to bring useful substances into the cell, other, less friendly particles may gain entry by the same route. Flu viruses, diphtheria, and cholera toxin all use receptor-mediated endocytosis pathways to gain entry into cells. EXOCYTOSIS Cells must take in certain molecules, such as nutrients, but they also need to release other molecules, such as signaling proteins and waste products, to the outside environment. Exocytosis (exo = external, cytosis = transport mechanism) is a form of bulk transport in which materials are transported from the inside to the outside of the cell in membrane-bound vesicles that fuse with the plasma membrane. Some of these vesicles come from the Golgi apparatus and contain proteins made specifically by the cell for release outside, such as signaling molecules. Other vesicles contain wastes that the cell needs to dispose of, such as the leftovers that remain after a phagocytosed particle has been digested. These vesicles are transported to the edge of the cell, where they can fuse with the plasma membrane and release their contents into the extracellular space. Some vesicles fuse completely with the membrane and are incorporated into it, while others follow the “kiss-and-run” model, fusing just enough to release their contents (“kissing” the membrane) before pinching off again and returning to the cell interior.