Regulation of membrane trafficking by Coronins

ABSTRACT The extensive family of the Coronins plays an important role in regulating the actin networks that drive cell migration, polarity, cell shape and intracellular trafficking, and thereby contribute to essential biological processes ranging from innate immunity to neuronal signaling. However, these functions and activities have been characterized for the canonical Coronins. In stark contrast, we know next to nothing about the cellular roles and actin cytoskeleton regulation of the structurally distinct class of the tandem Coronins, which comprises Coronin 7 (Coro7), POD-1, and CorB. Our preliminary data show that mammalian Coro7 can control Arp2/3-mediated nucleation, although the mechanism underlying this activity remains elusive. In addition, we show that this actin- regulatory activity can regulate NPF-induced actin networks that drive intracellular membrane transport, including autophagy, a process used by cells to dispose of unwanted organelles, misfolded proteins and toxic aggregates. Using a multidisciplinary approach comprising state-of-the-art biochemical, biophysical, genetic and live-imaging techniques we propose here to elucidate 1) how Coro7 structurally interacts with Arp2/3, 2) how Coro7 mechanistically inhibits Arp2/3-mediated nucleation by nucleation promoting factors, and 3) by other Arp2/3 regulators, and 4) how these actin-regulatory activities of Coro7 regulate the turnover of the branched actin networks that drive autophagy.