title: Myosin 1E localizes to actin polymerization sites in lamellipodia, affecting actin dynamics and adhesion formation.
abstract: Because the actin network in active lamellipodia is continuously assembling at the edge, moving inward and disassembling, there is a question as to how actin-binding proteins and other components are transported to the leading edge and how nascent adhesions are stabilized. Active transport could play a significant role in these functions but the components involved are unknown. We show here that Myosin 1E (a long tailed Myosin 1 isoform) rapidly moves to the tips of active lamellipodia and to actin-rich early adhesions, unlike Myosin 1G, 1B or 1C (short tailed isoforms). Myosin 1E co-localizes with CARMIL, FHOD1, Arp3 and β3-integrin in those early adhesions. But these structures precede stable paxillin-rich adhesions. Myosin 1E movement depends upon actin-binding domains and the presence of an SH3 oligomerization domain. Overexpression of a Myosin 1E deletion mutant without the extreme C-terminal interacting (SH3) domain (Myosin 1EΔSH3) increases edge fluctuations and decreases stable adhesion lifetimes. In contrast, overexpression of Myosin 1E full tail domain (TH1+TH2+TH3/SH3) decreases edge fluctuation. In Myosin 1E knockdown cells, and more prominently in cells treated with Myosin 1 inhibitor, cell-matrix adhesions are also short-lived and fail to mature. We suggest that, by moving to actin polymerization sites and early adhesion sites in active lamellipodia, Myosin 1E might play important roles in transporting not only important polymerizing proteins but also proteins involved in adhesion stabilization.
authors: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors: Prabuddha
authors: P
authors: Gupta
authors: Nils C
authors: NC
authors: Gauthier
authors: Yu
authors: Y
authors: Cheng-Han
authors: Yuan
authors: Y
authors: Zuanning
authors: Bruno
authors: B
authors: Pontes
authors: Malte
authors: M
authors: Ohmstede
authors: René
authors: R
authors: Martin
authors: Hans-Joachim
authors: HJ
authors: Knölker
authors: Hans-Günther
authors: HG
authors: Döbereiner
authors: Mira
authors: M
authors: Krendel
authors: Michael
authors: M
authors: Sheetz
keywords: Cell–matrix adhesion; Myosin 1E; Transport