Authors
Loic Fort, José Miguel Batista, Peter A Thomason, Heather J Spence, Jamie A Whitelaw, Luke Tweedy, Jennifer Greaves, Kirsty J Martin, Kurt I Anderson, Peter Brown, Sergio Lilla, Matthew P Neilson, Petra Tafelmeyer, Sara Zanivan, Shehab Ismail, David M Bryant, Nicholas CO Tomkinson, Luke H Chamberlain, Grant S Mastick, Robert H Insall, Laura M Machesky
Publication date
2018/10
Journal
Nature cell biology
Volume
20
Issue
10
Pages
1159-1171
Publisher
Nature Publishing Group UK
Description
Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion–retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar …
Scholar articles
L Fort, JM Batista, PA Thomason, HJ Spence… - Nature cell biology, 2018