RhoA effector mDia1 is required for PI 3-kinase-dependent actin remodeling and spreading by thrombin in platelets.
The RhoA effector mDia1 is involved in controlling the balance between filamentous and monomeric actin, but its role in modulating thrombin-induced actin remodeling and platelet spreading on fibrinogen matrices remains unclear. In this study, mDia1 was shown to translocate to the platelet cytoskeleton following thrombin stimulation, in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner. Anti-mDia1 loading or pretreatment with PI 3-kinase inhibitors essentially abrogated thrombin-elicited actin stress fiber formation, with a corresponding decrease in the proportion of platelets exhibiting a fully spread morphology. We also investigated the mechanisms underlying the effects of mDia1 on thrombin-induced actin remodeling and platelet spreading, and found that these involved PI 3-kinase-mediated induction of mDia1 interaction with RhoA. Collectively, these results suggest that the PI 3-kinase/RhoA/mDia1 axis is a critical pathway for coupling thrombin signaling to actin cytoskeletal remodeling during platelet spreading.
Gao
Guangxun
G
Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
Chen
Liang
L
Dong
Baoxia
B
Gu
Hongtao
H
Dong
Hongjuan
H
Pan
Yaozhu
Y
Gao
Ying
Y
Chen
Xiequn
X
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D000080865:Formins; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021381:Protein Transport; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000080865:Formins; D019869:Phosphatidylinositol 3-Kinases; D013917:Thrombin; D020742:rhoA GTP-Binding Protein; C108962:DIAPH1 protein, human; C066737:RHOA protein, human