WHAMM Directs the Arp2/3 Complex to the ER for Autophagosome Biogenesis through an Actin Comet Tail Mechanism

摘要: Nucleation-promoting factors (NPFs) control the spatio-temporal activity of Arp2/3 complex in cells]. Thus, WASP and WAVE direct formation branched actin networks at leading edge during cell motility endo/exocytosis, whereas WASH is involved endosomal transport. Less understood are WHAMM JMY, two NPFs with similar domain architecture. JMY found nucleus cytosol transcriptional regulation, motility, trans-Golgi was reported to bind microtubules be ER cis-Golgi Here, we show that directs for autophagosome biogenesis through an actin-comet tail mechanism. Macroautophagy--the process by which cytosolic material engulfed into autophagosomes degradation and/or recycling--was recently shown involve actin, but mechanism unknown. We forms puncta colocalize comigrate autophagy markers LC3, DFCP1, p62 a WHAMM-dependent Under starvation, observed interface between neighboring autophagosomes, whose number size increase expression. Interfering polymerization, inhibiting complex, knocking down WHAMM, or blocking its interaction mutagenesis all inhibit comet reduce autophagosomes. Finally, shows localization could processes. These results reveal link Arp2/3-complex-dependent assembly autophagy.