Myosin-X provides a motor-based link between integrins and the cytoskeleton.
Unconventional myosins are actin-based motors with a growing number of attributed functions. Interestingly, it has been proposed that integrins are transported by unidentified myosins to facilitate cellular remodelling. Here we present an interaction between the unconventional myosin-X (Myo10) FERM (band 4.1/ezrin/radixin/moesin) domain and an NPXY motif within beta-integrin cytoplasmic domains. Importantly, knock-down of Myo10 by short interfering RNA impaired integrin function in cell adhesion, whereas overexpression of Myo10 stimulated the formation and elongation of filopodia in an integrin-dependent manner and relocalized integrins together with Myo10 to the tips of filopodia. This integrin relocalization and filopodia elongation did not occur with Myo10 mutants deficient in integrin binding or with a beta(1)-integrin point mutant deficient in Myo10 binding. Taken together, these results indicate that Myo10-mediated relocalization of integrins might serve to form adhesive structures and thereby promote filopodial extension.
Zhang
Hongquan
H
Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology F46, Karolinska University Hospital Huddinge, SE-141 86 Huddinge, Sweden. hongquan.zhang@labmed.ki.se
Berg
Jonathan S
JS
Li
Zhilun
Z
Wang
Yunling
Y
Lång
Pernilla
P
Sousa
Aurea D
AD
Bhaskar
Aparna
A
Cheney
Richard E
RE
Strömblad
Staffan
S
D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009218:Myosins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D034622:RNA Interference
D019012:Integrin beta1; D016023:Integrins; C498718:MYO10 protein, human; C409064:Myo10 protein, mouse; D009218:Myosins