Abstract
SummaryBecause 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.
Highlights
Myosin 1 proteins are abundant actin-activated ATPases that are commonly monomeric when purified (Pollard and Korn, 1973)
Summary 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
We show here that Myosin 1E rapidly moves to the tips of active lamellipodia and to actinrich early adhesions, unlike Myosin 1G, 1B or 1C
Summary
Myosin 1 proteins are abundant actin-activated ATPases that are commonly monomeric (single headed) when purified (Pollard and Korn, 1973) Another feature of these Myosin 1 isoforms is their association with cell membrane by the Tail Homology 1 (TH1) domain, that contains a lipid-binding, PH like, domain (Hokanson et al, 2006; Patino-Lopez et al, 2010). Specialized actin rich structures like lamellipodia and filopodia are necessary components of migrating cells (Ridley et al, 2003) These structures need G-actin flow for actin polymerization at the tip and need proteins responsible for capping the barbed end of actin filaments and stabilization of newly formed matrix adhesions (Borisy and Svitkina, 2000; Mogilner and Keren, 2009; Schmidt et al, 1993; Small et al, 2002). We show, Myosin 1E dynamically localizes at the very tip of active actin rich lamellipodia and in stationary actin rich puncta that transiently appear behind the lamellipodial tip, containing
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