Module 17: Endocytosis PDF

MODULE 17 Slide 1: Endocytosis The cellular take-up of macromolecules, particulate substances, and cells. The material is enclosed by the plasma membrane, which invaginates and pinches off to form a vesicle. Types of endocytosis: phagocytosis, pinocytosis, receptor-mediated. Slide 2: Compone...

MODULE 17 Slide 1: Endocytosis The cellular take-up of macromolecules, particulate substances, and cells. The material is enclosed by the plasma membrane, which invaginates and pinches off to form a vesicle. Types of endocytosis: phagocytosis, pinocytosis, receptor-mediated. Slide 2: Components of the Endocytic Pathway Early endosomes (EE): pH ~6.3; receive endocytic vesicles with cargo and plasma membrane from the cell surface; endocytosed ligands dissociate from the receptors, some receptors are recycled. Late endosomes (LE): pH ~5.5, on their way to lysosomes, receive material from early endosomes, TGN, and phagosomes; contain lysosomal proteins. Lysosomes: pH ~4.8, with hydrolases; break down fats, carbohydrates, and proteins into simple compounds that are used in the cytoplasm for synthesis. Slide 3: Early and Late Endosomal Compartments In polarized epithelial cells, endocytosis occurs from the basolateral and apical domains. Endocytosed material enters the early endosomes unique to each domain. Endocytosed receptors are recycled to their original membrane domain unless they contain signals for transcytosis. Molecules endocytosed from either domain and not retrieved from the early endosomes end up in a common late endosomal compartment and are degraded in lysosomes. Slide 4: Multivesicular Bodies (MVB) Endosomes enclose invaginated membrane and internally pinch-off vesicles; MVBs fuse with late endosomes or other MVBs to become late endosomes. Transport lipids, proteins, and nucleic acids; the membrane proteins are degraded or recycled. Slide 5: Phagocytosis Ingestion of particles (microorganisms, dead cells) into phagosomes that eventually fuse with lysosomes. Professional phagocytes (macrophages, neutrophils, dendritic cells) and nonprofessional phagocytes exist. Initiated by the binding of phagocyte receptors to distinct molecular patterns on targets; binding induces actin polymerization at the site of ingestion, resulting in pseudopods. Triggers are antibodies bound to microorganisms, oligosaccharides on the surface of microorganisms. Slide 6: Pinocytosis Non-selective uptake of extracellular compounds into uncoated vesicles (macropinosomes) that fuse with lysosomes or do not mature beyond the early endosomal stage, and are recycled to the plasma membrane. Receptors activated by growth factors increase actin polymerization at the cell membrane; resulting in lamellipodia- induced ruffles that fold inwards and fuse with the basal membrane to form macropinosomes. Antigen-presenting cells "look for" antigens through constitutive pinocytosis; after internalization, the antigens are processed into peptides for presentation. Pinocytosis compared to phagocytosis: (1) "eating" versus "drinking", and (2) in phagocytosis, larger particles are engulfed than in pinocytosis. Slide 7: Caveolar Endocytosis Clathrin-independent, involves plasma membrane invaginations called caveolae. Caveolar coat is structured by specific proteins (caveolins, cavins). Caveolae may collect cargo proteins by virtue of the lipid composition of the caveolar membrane, rather than by the protein coat. Caveolae deliver contents to endosome-like compartments or through transcytosis to the plasma membrane on the opposite side of a polarized cell. Slide 8: Receptor-mediated Endocytosis The cargo binds to transmembrane receptors, accumulates in coated pits, and enters the cell in clathrin-coated vesicles. Some (but not all) receptors enter coated pits only if bound to ligands. The pits function as molecular filters, preferentially collecting certain receptors over others. There are more than 25 different receptors known to participate in this type of endocytosis. Examples include iron-bound transferrin recycling and the uptake of low-density lipoprotein (LDL).