Practice question

Barbed end availability determines where new polymerization occurs in lamellipodia and filopodia. CapZ heterodimer alpha beta forms cap with extremely low dissociation rate half life 30 minutes in vitro. Binding interface extensive, burying 2000 square angstroms, alpha C terminal tentacle interacting with hydrophobic cleft between actin subdomains 1 and 3 of ultimate subunit, beta tentacle contacting penultimate subunit groove, physically blocking monomer docking. Quantitative fluorescence speckle microscopy shows most barbed ends in resting cells are capped, only about 5 percent free, but seconds after stimulation by EGF uncapping factors CARMIL complex containing CPI motif binds CapZ weakening affinity 100 fold and PIP2 binding further destabilizes, freeing ends for Arp2/3 mediated branching and rapid protrusion. CapZ does not nucleate new filaments which requires Arp2/3 activation or formin dimer, does not sever filament, function distinct from cofilin gelsolin, and does not hydrolyze ATP, acting purely as high affinity terminator preventing polymerization at plus end important for remodeling.