QUIZ NOTES 3.pdf

STEPS: (1) Initiation of coat assembly. The coat components (in blue) are recruited to the donor compartment by binding to a membrane-associated GTPase (in red) and/or to a specific phosphoinositide. Transmembrane cargo proteins (receptors) and SNAREs begin to gather at the assembling coat. (2) Budd...

STEPS: (1) Initiation of coat assembly. The coat components (in blue) are recruited to the donor compartment by binding to a membrane-associated GTPase (in red) and/or to a specific phosphoinositide. Transmembrane cargo proteins (receptors) and SNAREs begin to gather at the assembling coat. (2) Budding. The membrane-distal coat components (green) are added and polymerize into a mesh-like structure. The cargo is concentrated, and the membrane curvature increases. (3) Scission. The neck between the vesicle and donor compartment is severed either by the direct action of the coat or accessory proteins. (4) Uncoating. The vesicle loses its coat due to various events including inactivation of the small GTPase, phosphoinositide hydrolysis, and the action of uncoating enzymes. The coat proteins are recycled for additional rounds of vesicle budding. (5) Tethering. The “naked” vesicle moves to the acceptor compartment, possibly guided by the cytoskeleton and it becomes tethered to the acceptor compartment by the combination of a Rab-GTP and tethering factors (effectors of Rab). (6) Docking. The v- and t-SNAREs assemble into a complex. (7) The trans-SNARE complex promotes the fusion of the vesicle and acceptor lipid bilayers. Cargo is transferred to the acceptor compartment, and the SNAREs are recycled. A single amino acid substitution (point mutation), leading to protein misfolding. Misfolded proteins accumulate in the ER due to improper folding and are subsequently degraded, preventing their normal function. - The mutation may destabilize the protein or mRNA, leading to defective protein synthesis. - The mutation may interfere with the ER signal sequence, preventing the protein from entering the ER. - It could cause a continuous ER/Golgi retrieval signal, keeping the protein trapped within the cell. - A lysosomal targeting signal could direct the mutated protein to lysosomes for degradation. To distinguish between these possibilities, immunofluorescence techniques can detect mutant proteins using antibodies, showing where the protein is located in the cell. - Rab proteins bind to specific effectors to assist in docking vesicles to target membranes. The information provided on Rab effectors is novel and not directly covered in the modules. - In the absence of Fe (ferrous/iron) ions, transferrin is free to circulate the blood and it does not bind its receptors. Once bound to iron, transferrin in the blood (at neutral pH) binds its receptor on the cell surface and is endocytosed. In the lower pH of endosomes, transferrin releases the Fe ions, but is still bound to the receptor, which is recycled back to the cell surface, where at neutral pH transferrin dissociates from the receptor. - Synaptic transmission, involving neurotransmitter release via exocytosis, requires vesicle membrane integration into the plasma membrane. If dynamin is defective, endocytosis is blocked, preventing vesicle retrieval from the membrane..