Figure 8. WHAMM promotes Arp2/3 complex-mediated actin assembly during autophagosomal membrane morphogenesis.

(A) HK-2 cells expressing LAP-WHAMM wild type or a LAP-WHAMM W807A mutant deficient in Arp2/3 activation (both in green) were fixed and stained with antibodies to LC3 (magenta) and actin (cyan). Scale bar, 10μm. (B) Model for WHAMM and Arp2/3 complex function in autophagosome closure during cargo capture. Aggregated protein cargo (gray) is ubiquitinated (green) prior to its engagement by autophagy receptors like p62 (orange). WHAMM (purple) and the Arp2/3 complex (blue) promote the assembly of actin filaments (red) necessary for autophagosome membrane morphogenesis. In the absence of WHAMM or the Arp2/3 complex, actin assembly at autophagic membranes is abrogated, resulting in inefficient receptor engagement and autophagosome closure.