The integrin α6β1 modulation of PI3K and Cdc42 activities induces dynamic filopodium formation in human platelets

Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, 112, Taiwan.
Journal of Biomedical Science (Impact Factor: 2.76). 01/2006; 12(6):881-98. DOI: 10.1007/s11373-005-9021-2
Source: PubMed


Platelets are an ideal model for studying a rapid morphological change in response to various signal transduction systems. Morphological changes via the activation of integrin alphaIIbbeta3 in platelets have been investigated intensively. In contrast, activation via integrin alpha6beta1 is less well studied. Here, we provide the first biochemical evidence that integrins alpha6beta1 and alphaIIbbeta3 of platelets are associated with different membrane proteins. We also demonstrate that platelets activated by integrin alpha6beta1 show dynamic change by actively forming filopodia and never fully spreading over a period of more than an hour. In addition, platelets activated by integrin alpha6beta1 are different from those activated by integrin alphaIIbbeta3 in terms of cell-substrate contact and in their distribution pattern of actin, Arp2/3 and various phosphotyrosine proteins. The morphological appearance of platelets produced through integrin alpha6beta1 activation is highly dependent on PI3 kinase (PI3K) but less dependent on Src kinase. Suppression of PI3K activity in integrin alpha6beta1 activated platelets induces an increase in Cdc42 activity and more filopodium formation. However, both Cdc42 and PI3K activity are higher in platelets activated by integrin alpha6beta1 than in those activated by integrin alphaIIbbeta3. Taken together, this study demonstrates that the signals induced by integrin alpha6beta1 modulate at the level of PI3K and Cdc42 activity to allow platelets to actively form filopodia.

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Available from: Hsin-Hou Chang, Aug 07, 2015
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    • "Although platelets express at least five different integrins, most of our understanding on the contribution of PI3K is related to studies on the two major receptors: integrin a IIb b 3 and integrin a 2 b 1 . Indeed, to our knowledge the investigation of the possible involvement of PI3K in platelet activation induced by other integrin receptors is limited to the work of Chang and collaborators, who demonstrated the importance of PI3K for integrin a 6 b 1 -mediated filipodia formation (Chang et al., 2005). "
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