Practice question

Endocytosis of cargo such as EGFR transferrin requires actin assistance in mammalian cells against high membrane tension especially under high membrane stiffness. Clathrin coated pit maturation involves transient actin patch assembly lasting 10 to 20 seconds around neck. Key signaling axis Cdc42 GTP recruits N WASP, which in resting state autoinhibited by intramolecular interaction between basic region GBD and VCA. Activation occurs when Cdc42 GTP binds GBD, PIP2 binds basic region, and SH3 proteins TOCA1 syndapin bind proline rich stretch, releasing VCA. Free VCA binds one G actin via WH2 and Arp2/3 via acidic region bringing complex to side of preexisting filament. Branch nucleation at 70 degrees generates pushing force assisting invagination and cooperates with dynamin GTPase for scission. Cells from Wiskott Aldrich syndrome patients lacking functional WASP show defective TCR endocytosis and actin foci. Formins create unbranched filaments elsewhere, myosin I provides tension but not activation, CapZ restricts growth. Thus WASP family as WASp functions as initiator activating Arp2/3 to drive actin assembly during receptor mediated endocytosis and vesicle formation.