The integrin alpha6beta1 modulation of PI3K and Cdc42 activities induces dynamic filopodium formation in human platelets.
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.
Chang
Jui-Chin
JC
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, 112, Taiwan.
Chang
Hsin-Hou
HH
Lin
Chien-Ting
CT
Lo
Szecheng J
SJ
D051377:Actin-Related Protein 2 / Q000737:chemistry; D051378:Actin-Related Protein 3 / Q000737:chemistry; D000199:Actins / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D039121:Integrin alpha6beta1 / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019000:Phosphotyrosine / Q000737:chemistry; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D039121:Integrin alpha6beta1; D007797:Laminin; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C072026:rhodostomin; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein