Zaidi Lecture 9/28 Trafficking Flashcards
Lysosomes
Membrane enclosed compartments filled with hydrolytic enzymes; important for intracellular digestion of macromolecules; derived from late endosomes
Vacuolar ATPase Pump
Pumps H+ ions into lysosomes to maintain the acidic pH and to drive transport of small metabolites
Transport from Trans Golgi Network to Lysosomes
Pathway that delivers membrane proteins and hydrolases to lysosomes
Sorting Signal for Lysosomal Hydrolases
Mannose-6-phosphate, which is attached in the Cis Golgi Network; M6P receptors in Trans Golgi Network recognize the sugar to be packaged into clathrin coated vesicles that bud off from TGN
Hurler’s Disease
Mutation in the enzyme required to break down glycosaminoglycan chains
Inclusion Cell Disease
All of the lysosomal hydrolases are missing in many cell types; undigested substrates accumulate as “inclusions”
Endocytosis
Uptake of macromolecules from exterior across plasma membrane; material is progressively enclosed by a portion of plasma membrane
Phagocytosis
Large particles ingested by vesicles called phagosomes; carried out by phagocytes, macrophages, neutrophils; phagosomes fuse with lysosomes and ingested material is degraded; undigested material secreted out by exocytosis
Pinocytosis
Small particles ingested by pinocytic vesicles; occurs continuously in all eukaryotic cells
Receptor-mediated Endocytosis
Used to import select macromolecules from outside cell; uptake of cholesterol is done in this way; blockage of this pathway results in atherosclerosis
GLUT 4
Glucose transporter 4; only one that is insulin sensitive
Exocytosis
Transport vesicles move from TGN to plasma membrane; membrane proteins and lipids in the vesicles are destined for plasma membrane while soluble proteins are secreted out of cells
Constitutive Secretory Pathway
Operates continuously
Regulated Secretory Pathway
Triggered by signals
Process of Endocytosis
- Material is progressively enclosed by a portion of the plasma membrane
- Plasma membrane invaginates and then pinches off to form endocytic vesicle
Process of Receptor-mediated Endocytosis
- Molecules bind to receptors on membrane surface
- Accumulate in clathrin-coated pits
- Enter cell as receptor-macromolecular complex in clathrin-coated vesicles
- Provides selective concentration mechanism
Process of Phagocytosis
- Triggered by binding of particle to receptors on phagocyte surface
- Receptors functionally linked to cellular response machinery
- Antibodies bind to microbe, Fc chain recognized by Fc receptor on surface of macrophages/neutrophils
- Binding triggers formation of pseudopod which engulfs the particle and forms phagosome
- Pseudopod formation driven by localized actin polymerization and reorganization
- Controlled by Rho GTPases and phosphoinositide signaling
Process of Pinocytosis
- Process begins at clathrin-coated pits
- Membrane invaginates and pinches off to form clathrin-coated vesicle
- Extracellular fluid with various solutes trapped in pits as they invaginate
Process of Pinocytosis through Caveolae
- Caveolae invaginate into membrane by virtue of lipid composition and not the protein coat
- Caveolae pinch off from plasma membrane by dynamin to form caveosome (endosome-like compartment)
* DO NOT CONNECT WITH LYSOSOMES*
Caveolae
Flask-shaped invaginations in plasma membrane enriched in cholesterol and glycosphingolipids and GPI-anchored membrane proteins; major structural protein is caveolin
Formation of Secretory Vesicles
Proteins destined for secretion packed into secretory vesicles in TGN
Involves selective aggregation/clumping of proteins, but mechanism not fully understood
Vesicle membrane proteins may have receptors for aggregated proteins or undergo phagocytosis like mechanism
