G proteins G12 and G13 control the dynamic turnover of growth factor-induced dorsal ruffles.
Growth factors induce massive actin cytoskeletal remodeling in cells. These reorganization events underlie various cellular responses such as cell migration and morphological changes. One major form of actin reorganization is the formation and disassembly of dorsal ruffles (also named waves, dorsal rings, or circular ruffles). Dorsal ruffles are involved in physiological functions including cell migration, invasion, macropinocytosis, plasma membrane recycling, and others. Growth factors initiate rapid formation (within 5 min) of circular membrane ruffles, and these ruffles move along the dorsal side of the cells, constrict, close, and eventually disassemble ( approximately 20 min). Considerable attention has been devoted to the mechanism by which growth factors induce the formation of dorsal ruffles. However, little is known of the mechanism by which these ruffles are disassembled. Here we have shown that G proteins G(12) and G(13) control the rate of disassembly of dorsal ruffles. In Galpha(12)(-/-)Galpha(13)(-/-) fibroblast cells, dorsal ruffles induced by growth factor treatment remain visible substantially longer ( approximately 60 min) than in wild-type cells, whereas the rate of formation of these ruffles was the same with or without Galpha(12) and Galpha(13). Thus, Galpha(12)/Galpha(13) critically regulate dorsal ruffle turnover.
Wang
Dawei
D
Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, USA.
Tan
Ying-cai
YC
Kreitzer
Geri E
GE
Nakai
Yoko
Y
Shan
Dandan
D
Zheng
Yi
Y
Huang
Xin-Yun
XY
D000199:Actins / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009154:Mutation; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D013997:Time Factors
D000199:Actins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D049452:Green Fluorescent Proteins; D000077214:Becaplermin; D044365:GTP-Binding Protein alpha Subunits, G12-G13