Cell Membrane & Vesicular Transport PDF

1 Cell membrane& vesicular Transport ILOs By the end of this lecture, students will be able to 1. Relate the molecular structure of membrane lipids to its different membrane functions. 2. Correlate the variable peripheral & integral membrane molecules to membrane function. 3. Int...

1 Cell membrane& vesicular Transport ILOs By the end of this lecture, students will be able to 1. Relate the molecular structure of membrane lipids to its different membrane functions. 2. Correlate the variable peripheral & integral membrane molecules to membrane function. 3. Interpret the diagrammatic presentation of the fluid mosaic model 4. Interpret endocytosis & exocytosis as vital processes for transport across the cell membrane. 5. Differentiate between types of endocytosis in normal and pathological conditions. Cell Components The cell is composed of two basic parts: cytoplasm (Gr. kytos, cell, + plasma, thing formed) and nucleus. Individual cytoplasmic components are usually not clearly distinguishable in common hematoxylin and eosin-stained preparations; the nucleus, however, appears intensely stained dark blue or black. (Why?) Cytoplasm The outermost component of the cell, separating the cytoplasm from its extracellular environment, is the plasma membrane (plasmalemma). However, even if the plasma membrane is the external limit of the cell, there is a continuum between the interior of the cell and extracellular macromolecules. The cytoplasm is composed of a matrix, or cytosol, in which are embedded the organelles, the cytoskeleton, and deposits of carbohydrates, lipids, and pigments. Higher levels of organization Plasma Membrane All eukaryotic cells are enveloped by a limiting membrane composed of phospholipids, cholesterol, proteins, and chains of oligosaccharides covalently linked to phospholipids and protein molecules. The cell, or plasma, membrane functions as a selective barrier that Page 1 of 5 regulates the passage of certain materials into and out of the cell and facilitates the transport of specific molecules. One important role of the cell membrane is to keep constant the intracellular milieu, which is different from the extracellular fluid. Membranes also carry out a number of specific recognition and regulatory functions (to be discussed later), playing an important role in the interactions of the cell with its environment. Membranes range from 7.5 to 10 nm in thickness and consequently are visible only in the electron microscope (so, what is visible on the light microscope?) Molecular structure of the cell membrane (Figure 2) 1- Membrane phospholipids. Structure: two long, nonpolar (hydrophobic) hydrocarbon chains linked to a charged (hydrophilic) head group. (Why it appears black in electron micrograph? Is it a single line?) o Organization: the hydrophobic (nonpolar) chains directed toward the centre of the membrane and the hydrophilic (charged) heads directed outward. o Cholesterol is also a constituent of cell membranes. Role of cholesterol; (It will be discussed later with fluidity of the membrane). Note: ✔ This represents the fluid mosaic model of the cell membrane. ✔ The lipid composition of each half of the bilayer could be different according to its functional role. ✔ The trilaminar appearance are characteristic of all the internal cellular membranes (eg. Nuclear, mitochondrial, and endoplasmic reticulum) as well as the plasma membrane. ✔ Some of the lipids, known as glycolipids, possess oligosaccharide chains that extend outward from the surface of the cell membrane and thus contribute to lipid asymmetry. (Figure 2) 2- Proteins, About 50% of the plasma membrane components Types: Page 2 of 5  o Integral proteins are directly incorporated within the lipid bilayer. Some integral proteins span the membrane one or more times, from one side to the other. Other proteins are large enough to extend across the two lipid layers and protrude from both membrane surfaces (transmembrane proteins). Integrins are transmembrane proteins that are linked to cytoplasmic cytoskeletal filaments and to extracellular molecules. Through these linkages there is a constant exchange of influence, in both ways, between the extracellular matrix and the cytoplasm. o Peripheral proteins exhibit a looser association with membrane surfaces. They may protrude from either the outer or inner surface. o Organelle-specific membranes proteins confer unique functions on certain organelles. Correlate the functional forms of integral membrane protein in Fig. 2 with its type. 3- The carbohydrate moieties of glycoproteins and glycolipids exoplasmic domain; they are important components of specific molecules called receptors that participate in important interactions such as cell adhesion, recognition, and response to protein hormones. As with lipids, the distribution of membrane proteins is different in the two surfaces of the cell membranes. Therefore, all membranes in the cell are asymmetric. Glycocalyx (cell coat) In the electron microscope the external surface of the cell shows a fuzzy carbohydrate-rich region called the glycocalyx. This layer is composed of carbohydrate chains linked to membrane proteins and lipids and of cell-secreted glycoproteins and proteoglycans. Functional significance of glycocalyx The glycocalyx has a role in cell recognition and attachment to other cells and to extracellular molecules. Transport across the cell membrane Movement of molecules and ions across membranes occurs by different mechanisms including: a. Passive transport (simple and facilitated diffusion). b. Active transport (pump and cotransport carrier). (Fig 3) c. Bulk movement of materials into and out of the cells (endocytosis & exocytosis) which will be discussed in this section. Mass transfer of material also occurs through the plasma membrane. This bulk uptake of material is known as endocytosis. The corresponding name for release of material in bulk is exocytosis. However, at the molecular level, exocytosis and endocytosis are different processes that utilize different protein molecules. Page 3 of 5 Endocytosis: (Gr. endon, within, + kytos, cell) The process whereby a cell ingests macromolecules, particulate matter, and other substances from the extracellular space. Mechanisms of endocytosis: (Figure 3) 1. Phagocytosis (cell eating) It is a nonselective process of engulfing larger particulate matter, such as microorganisms, cell fragments, and degenerated cells (e.g., defunct red blood cells), by specialized cells known as phagocytes. The engulfed material is enclosed in a vesicle called the phagosome. 2. Pinocytosis Nonselective process where small invaginations of the cell membrane form and entrap extracellular fluid forming a pinocytotic vesicle that pinch off from the cell surface and may fuse with lysosomes (see the section on Lysosomes later in this chapter). Receptor-Mediated Endocytosis It is a selective process that involves engulfment of macromolecules. This process depends on interaction between two structures: ⮚ Receptor proteins (cargo receptors) in the cell membrane. Cargo receptors are transmembrane proteins. ⮚ Macromolecules (ligands), (What is ligand?) such as low-density lipoproteins and protein hormones that bind with its receptor on the cell membrane. The receptors are either originally widely dispersed over the surface or aggregated in special regions called coated pits. Binding of the ligand to its receptor causes widely dispersed receptors to accumulate in coated pits. The coated pit invaginates and pinches off from the cell membrane, forming a coated vesicle that carries both the ligand and its receptor into the cell. Page 4 of 5 Note: Caveolae is a special form of endocytosis where the coating protein is caveolin (will be discussed later) Fate of the endocytotic vesicle (Figure 4) ⮚ The coated vesicles soon lose their clathrin coat and fuse with early endosomes near the periphery of the cell, a system of vesicles and tubules located in the cytosol near the cell surface. The clathrin molecules separated from the coated vesicles are moved back to the cell membrane to participate in the formation of new coated pits. ⮚ If some contents of the early endosome require degradation, they are transferred deeper in the cytoplasm into the late endosome. This similar set of tubules and vesicles, located deeper in the cytoplasm near the Golgi apparatus, helps to prepare its contents for eventual destruction by lysosomes. ⮚ The membranes of all endosomes contain ATP-linked H+ pumps that acidify the interior of the endosomes by actively pumping H+ ions into the interior of the endosome. Fate of the Endosome contents ⮚ Receptors that are separated from their ligand by the acidic pH of the early endosomes may return to the cell membrane to be reused. For example, low-density lipoprotein receptors are recycled several times. ⮚ The ligands typically are transferred to late endosomes. However, some ligands are returned to the extracellular milieu to be used again. An example of this activity is the iron-transporting protein transferrin. Occasionally, both the receptor and the ligand (e.g., epidermal growth factor and its receptor) are transferred to the late endosome, and then to a lysosome, for eventual degradation. (Fig 4) Fig. 4 Formation of early & late endosomes Page 5 of 5