High impact information on MYO10

• Myosin X regulates netrin receptors and functions in axonal path-finding [1].
• We report here that myosin-X (Myo10 or M10), the founding member of a novel class of myosins, localizes to the tips of filopodia and undergoes striking forward and rearward movements within filopodia, which we term intrafilopodial motility [2].
• May the force be with you: Myosin-X in phagocytosis [3].
• Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner [4].
• Furthermore, myosin X and the microtubule plus-end-tracking protein EB1 are shown to play a role in this mechanism through remodeling of actin cytoskeleton and stabilization of astral microtubules, respectively [4].

Biological context of MYO10

• Because unconventional myosins participate in cellular processes ranging from membrane trafficking to signaling and cell motility, myosin X is an attractive CLP target [5].
• Altered myosin X regulation in (tumor) cells lacking CLP may have as yet unknown consequences for cell growth and differentiation [5].
• This up-regulation occurs at the protein level by stabilization of myosin-10 [6].
• This increase in wound healing capacity was prevented by small interference RNA-mediated down-regulation of myosin-10 [6].

Anatomical context of MYO10

• Myosin X transports Mena/VASP to the tip of filopodia [7].
• We show here that siRNA-mediated knockdown of Myo10 in HeLa cells leads to a dramatic loss of dorsal filopodia [8].
• We also show that expressing Myo10 in COS-7 cells, a cell line that normally lacks dorsal filopodia, leads to a massive induction of dorsal filopodia [8].

Associations of MYO10 with chemical compounds

• Consistent with this observation, a Myo10 construct that lacks the FERM domain, the region that binds to integrin, retains the ability to induce dorsal filopodia [8].
• However, the rate constants for formation and dissociation of the myosin X MgAMPPNP complex were reduced 200-fold; the logarithm of the dissociation rate was roughly proportional to the fractional concentration of ethylene glycol [9].

Physical interactions of MYO10

• Yeast two-hybrid screening yielded a CLP-interacting clone encoding the three light chain binding IQ motifs of human "unconventional" myosin X. Pull-down experiments showed CLP binding to the IQ domain to be direct and Ca(2+)-dependent [5].

Co-localisations of MYO10

• Epitope-tagged myosin X was localized preferentially at the cell periphery in MCF-7 cells, and CLP colocalized with myosin X in these cells [5].

Other interactions of MYO10

• The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X [5].
• Additional experiments on the mechanism of Myo10 action indicate that it acts downstream of Cdc42 and can promote filopodia in the absence of VASP proteins [8].
• Myosin Ic and myosin X seem to be key players in extending and closing phagocytic-cup pseudopod [10].

Analytical, diagnostic and therapeutic context of MYO10

• Fluorescence microscopy and Western blotting revealed that CLP expression results in up-regulation of its target protein, myosin-10 [6].

References