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PMID:16894163

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Citation

Bohil, AB, Robertson, BW and Cheney, RE (2006) Myosin-X is a molecular motor that functions in filopodia formation. Proc. Natl. Acad. Sci. U.S.A. 103:12411-6

Abstract

Despite recent progress in understanding lamellipodia extension, the molecular mechanisms regulating filopodia formation remain largely unknown. Myo10 is a MyTH4-FERM myosin that localizes to the tips of filopodia and is hypothesized to function in filopodia formation. To determine whether endogenous Myo10 is required for filopodia formation, we have used scanning EM to assay the numerous filopodia normally present on the dorsal surfaces of HeLa cells. We show here that siRNA-mediated knockdown of Myo10 in HeLa cells leads to a dramatic loss of dorsal filopodia. Overexpressing the coiled coil region from Myo10 as a dominant- negative also leads to a loss of dorsal filopodia, thus providing independent evidence that Myo10 functions in filopodia formation. 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. Because the dorsal filopodia induced by Myo10 are not attached to the substrate, Myo10 can promote filopodia by a mechanism that is independent of substrate attachment. 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. Deletion of the MyTH4-FERM region, however, completely abolishes Myo10's filopodia-promoting activity, as does deletion of the motor domain. 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. Together, these data demonstrate that Myo10 is a molecular motor that functions in filopodia formation.

Links

PubMed PMC1567893 Online version:10.1073/pnas.0602443103

Keywords

Animals; COS Cells; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Cercopithecus aethiops; HeLa Cells/cytology; HeLa Cells/ultrastructure; Humans; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Molecular Motor Proteins/genetics; Molecular Motor Proteins/metabolism; Myosins/genetics; Myosins/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism; Pseudopodia/metabolism; Pseudopodia/ultrastructure; RNA, Small Interfering/genetics; RNA, Small Interfering/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; cdc42 GTP-Binding Protein/genetics; cdc42 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYO10

involved_in

GO:0051489: regulation of filopodium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYO10

involved_in

GO:0008360: regulation of cell shape

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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