Cell Biology: The Nucleus

• The nucleus houses most of the genes in eukaryotic cells, while ribosomes use DNA information to make proteins

The Nucleus: Information Central

• The nucleus is usually the most conspicuous organelle, averaging about 5 µm in diameter
• It is enclosed by the nuclear envelope, which separates its contents from the cytoplasm
• The nuclear envelope is a double membrane, each a lipid bilayer with associated proteins, separated by a 20-40 nm space
• Pore structures perforate the envelope, measuring about 100 nm in diameter
• An intricate protein structure, the pore complex, lines each pore and regulates protein, RNA, and macromolecule complex entry and exit
• The nuclear lamina, a net-like array of protein filaments, lines the nuclear side of the envelope and maintains its shape by mechanically supporting it
• A nuclear matrix, a framework of protein fibers, extends throughout the nuclear interior and helps organize genetic material
• DNA is organized into chromosomes within the nucleus, which carry genetic information
• Each chromosome contains one long DNA molecule associated with proteins, including histones
• Some proteins coil the DNA molecule of each chromosome, reducing its length to fit inside the nucleus
• The complex of DNA and proteins making up chromosomes is called chromatin
• Stained chromatin appears as a diffuse mass in micrographs when a cell is not dividing
• As a cell prepares to divide, chromosomes condense, becoming thick enough to be distinguished under a microscope
• Eukaryotic species have a characteristic number of chromosomes like human cells having 46 chromosomes
• The exceptions are human sex cells (eggs and sperm), which have only 23 chromosomes
• A fruit fly cell has 8 chromosomes in most cells and 4 in sex cells
• A prominent structure within the nondividing nucleus is the nucleolus, where ribosomal RNA (rRNA) is synthesized from DNA genes
• Proteins imported from the cytoplasm are assembled with rRNA into large and small subunits of ribosomes in the nucleolus
• These subunits exit the nucleus through nuclear pores to the cytoplasm, where they assemble into a ribosome
• The number of nucleoli depends on the species and the stage in the cell's reproductive cycle
• Nucleoli may play a role in controlling cell division and the life span of a cell
• The nucleus directs protein synthesis by synthesizing messenger RNA (mRNA), which carries information from the DNA
• mRNA is transported to the cytoplasm via nuclear pores where ribosomes translate the mRNA's genetic message into a specific polypeptide's primary structure

Ribosomes: Protein Factories

• Ribosomes are complexes made of ribosomal RNAs and proteins, and carry out protein synthesis
• They are not membrane-bounded and are not considered organelles
• Cells with high rates of protein synthesis have large numbers of ribosomes and prominent nucleoli for ribosome assembly
• Ribosomes build proteins in two cytoplasmic regions being either free or bound
• At any time, free ribosomes are suspended in the cytosol, while bound ribosomes are attached to the outside of the endoplasmic reticulum or nuclear envelope
• Bound and free ribosomes are structurally identical, and can play either role at different times
• Most proteins made on free ribosomes function within the cytosol, like enzymes that catalyze the first steps of sugar breakdown
• Bound ribosomes make proteins destined for insertion into membranes, for packaging within organelles like lysosomes, or for export from the cell, like digestive enzymes
• Cells specializing in protein secretion have a high proportion of bound ribosomes

The Endomembrane System

• The endomembrane system regulates protein traffic and performs metabolic functions
• It consists of the nuclear envelope, endoplasmic reticulum Golgi apparatus, lysosomes, various kinds of vesicles and vacuoles and the plasma membrane
• It carries out protein synthesis, protein transport into membranes and organelles or out of the cell, metabolism including lipid metabolism
• Membranes in this system are related through direct physical continuity or membrane segment transfer as vesicles
• Despite these relationships, the various membranes are not identical in structure and function
• The membrane thickness, molecular composition and types of chemical reactions carried out in a given membrane are not fixed, but can be modified several times during the membrane's life
• Consists of the endoplasmic reticulum and other endomembranes

The Endoplasmic Reticulum (ER): Biosynthetic Factory

• The endoplasmic reticulum (ER) is an extensive network of membranes and accounts for more than half the total membrane in eukaryotic cells
• Endoplasmic means "within the cytoplasm," and reticulum is "little net"
• The ER has membranous tubules and sacs called cisternae, which separates the ER lumen from the cytosol
• The ER membrane is continuous with the nuclear envelope, the space between the two membranes of the envelope is continuous with the ER lumen
• There are two distinct, though connected, regions of the ER that differ in structure and function: smooth ER and rough ER
• The smooth ER lacks ribosomes, while the rough ER is studded with ribosomes on the outer surface of the membrane
• Ribosomes are also attached to the cytoplasmic side of the nuclear envelope's outer membrane, which is continuous with rough ER

Functions of Smooth ER

• Smooth ER functions in diverse metabolic processes, including lipid synthesis, carbohydrate metabolism, drug and poison detoxification, and calcium ion storage
• Enzymes of the smooth ER synthesize lipids, including oils, steroids, and new membrane phospholipids
• Steroids produced include sex hormones of vertebrates and steroid hormones secreted by the adrenal glands
• Hormone-synthesizing cells are rich in smooth ER
• Smooth ER enzymes help detoxify drugs and poisons, especially in liver cells by adding hydroxyl groups to drug molecules to make them more water-soluble
• The sedative phenobarbital and other barbiturates are metabolized by smooth ER in liver cells
• Barbiturates, alcohol, and other drugs induce smooth ER proliferation and its detoxification enzymes, thus increasing the rate of detoxification
• This increases tolerance to the drugs, requiring higher doses for a particular effect
• Because some detoxification enzymes have a broad action, smooth ER proliferation in response to one drug can increase the need for higher dosages of other drugs as well
• The smooth ER stores calcium ions to trigger some responses, like secretion of vesicles carrying proteins

Functions of Rough ER

• Many cells secrete proteins produced by ribosomes attached to rough ER like pancreatic cells synthesize protein insulin
• As a polypeptide chain grows from a bound ribosome, the chain is threaded into the ER lumen through a protein complex in the ER membrane
• The new polypeptide folds into its functional shape as it enters the ER lumen
• Most secretory proteins are glycoproteins, proteins with carbohydrates covalently bonded to them by ER membrane enzymes
• ER membrane keeps secretory proteins separate from cytosol proteins, which are produced by free ribosomes
• Secretory proteins depart from the ER wrapped in the membranes of vesicles that bud like bubbles from transitional ER
• Vesicles in transit from one part of the cell to another are called transport vesicles
• Rough ER grows in place by adding membrane proteins and phospholipids to its own membrane, is a membrane factory
• Polypeptides destined to be membrane proteins are inserted into the ER membrane itself and anchored there by their hydrophobic portions
• Like the smooth ER, the rough ER also makes membrane phospholipids via enzymes
• The ER membrane expands, and portions of it are transferred as transport vesicles to other components of the endo-membrane system

The Golgi Apparatus: Shipping and Receiving Center

• Transport vesicles travel to the Golgi apparatus from the ER
• The Golgi apparatus acts as a warehouse for receiving, sorting, shipping, and some manufacturing
• Products of the ER, such as proteins, are modified, stored, and then sent to other destinations
• The Golgi consists of flattened membranous sacs called cisternae grouped in an associated stack and not physically connected
• A cell may have many stacks that separates its internal space from the cytosol
• Vesicles concentrated in the vicinity of the Golgi apparatus are engaged in the transfer of material between parts of the Golgi and other structures
• A Golgi stack has a structural directionality, with the membranes of cisternae on opposite sides of the stack differing in thickness and molecular composition
• The two sides of a Golgi stack are referred to as the cis face and the trans face, these receiving and shipping departments respectively
• The cis face is located near the ER, receiving transport vesicles moving material from the ER to the Golgi apparatus to fuse with a Golgi membrane
• The trans face gives rise to vesicles that pinch off and travel to other sites
• Products of the endoplasmic reticulum are usually modified during their transit from the cis region to the trans region of the Golgi apparatus like glycoproteins having carbohydrates first in the ER itself, and then as they pass through the Golgi
• The Golgi removes some sugar monomers and substitutes others, producing a large variety of carbohydrates and alters membrane phospholipids
• The Golgi apparatus also manufactures some macromolecules like polysaccharides
• These are secreted products, like pectins and noncellulose polysaccharides, in plant cells and releases it along with cellulose into their cell walls
• Nonprotein Golgi products in transport vesicles are inside transport vesicles that eventually fuse with the plasma membrane and adds to the surface area
• The Golgi manufactures and refines its products in stages, with different cisternae containing unique teams of enzymes
• The cisternae of the Golgi progress from the cis to the trans face, carrying and modifying their cargo as they move

Lysosomes: Digestive Compartments

• A lysosome is a membranous sac of hydrolytic enzymes that many eukaryotic cells use to digest macromolecules
• Lysosomal enzymes work best in the acidic environment found in lysosomes
• If a lysosome breaks open, the released enzymes are not very active and excessive leakage can destroy a cell by self-digestion
• Hydrolytic enzymes and the lysosomal membrane are made by rough ER and then transferred to the Golgi apparatus for further processing
• Three-dimensional shapes of inner surface and digestive enzymes spares from being destroyed
• Lysosomes carry out intracellular digestion that unicellular protists eat by engulfing smaller organisms or food particles, a process called phagocytosis
• The food vacuole fuses with a lysosome, whose enzymes digest the food with products pass into the cytosol and become nutrients for the cell
• Macrophages are a human cell that helps defend the body by engulfing and destroying bacteria and other invaders
• Lysosomes recycle the cell's own organic material, a process called autophagy
• During autophagy, a damaged organelle is surrounded by a double-membrane which fuses and lysosomal enzymes dismantle inner parts and organic compounds are released for reuse
• The cells of people with inherited lysosomal storage diseases lack a functioning hydrolytic enzyme, cause engorgement
• A lipid-digesting enzyme is missing or inactive in Tay-Sachs disease and the brain becomes impaired by a lipid buildup

Vacuoles: Diverse Maintenance Compartments

• Vacuoles are large vesicles derived from the endoplasmic reticulum and Golgi apparatus
• They integrate into a cell's endomembrane and like other membranes, are selective in transporting solutes resulting in differing vacuole composition compared to the cytosol
• Vacuoles perform a variety of functions in different kinds of cells
• Food vacuoles , from phagocytosis
• Contractile vacuoles pump excess water out of cells like protists maintaining concentration
• Other vacuoles carry out enzymatic hydrolysis, a shared function in animal cells with lysosomes
• In plants, small vacuoles can hold reserves of important organic compounds or protect against herbivores to store compounds that poisonous or unpalatable
• Other plant vacuoles contain pigments, that help attracts pollinating insects flowers
• Mature plant cells generally contain a large central vacuole, which develops by the coalescence of smaller vacuoles
• The solution inside the central vacuole is the plant cell's main repository of inorganic ions and plays a major role in the growth of plant cells, which enlarge as the vacuole absorbs water

The Endomembrane System: A Review

• The endomembrane system shows the flow of membrane lipids and proteins through the various organelles
• As the membrane moves from the ER to the Golgi and then elsewhere, its molecular composition and metabolic functions are modified
• The endomembrane system is a complex and dynamic player in the cell's compartmental organization
• Some organelles outside the endomembrane system play roles in energy transformations