WHAMM links actin assembly via the Arp2/3 complex to autophagy.
Macroautophagy (hereafter autophagy) is the process by which cytosolic material destined for degradation is enclosed inside a double-membrane cisterna known as the autophagosome and processed for secretion and/or recycling. This process requires a large collection of proteins that converge on certain sites of the ER membrane to generate the autophagosome membrane. Recently, it was shown that actin accumulates around autophagosome precursors and could play a role in this process, but the mechanism and role of actin polymerization in autophagy were unknown. Here, we discuss our recent finding that the nucleation-promoting factor (NPF) WHAMM recruits and activates the Arp2/3 complex for actin assembly at sites of autophagosome formation on the ER. Using high-resolution, live-cell imaging, we showed that WHAMM forms dynamic puncta on the ER that comigrate with several autophagy markers, and propels the spiral movement of these puncta by an Arp2/3 complex-dependent actin comet tail mechanism. In starved cells, WHAMM accumulates at the interface between neighboring autophagosomes, whose number and size increases with WHAMM expression. Conversely, knocking down WHAMM, inhibiting the Arp2/3 complex or interfering with actin polymerization reduces the size and number of autophagosomes. These findings establish a link between Arp2/3 complex-mediated actin assembly and autophagy.
a Department of Physiology ; Perelman School of Medicine; University of Pennsylvania ; Philadelphia , PA USA.
David J
DJ
Kast
a Department of Physiology ; Perelman School of Medicine; University of Pennsylvania ; Philadelphia , PA USA.
Roberto
R
Dominguez
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008958:Models, Molecular; D010588:Phagosomes / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins
Arp2/3 complex; actin cytoskeleton; macroautophagy; nucleation promoting factor