Mechanical stress regulates syndecan-4 expression and redistribution in vascular smooth muscle cells.
Syndecan-4 is a unique membrane-associated heparan sulfate proteoglycan that colocalizes with integrin heterodimers in focal adhesion complexes. Because focal adhesions serve as a putative mechanotransduction system, we postulated that physical forces that are sensed by focal adhesions may regulate the expression and intracellular distribution of syndecan-4 and thereby modulate cell movement and orientation. In this report, syndecan-4 was identified as a transcriptionally regulated, immediate-early gene in response to the application of oscillatory stress. This fluctuation was associated with coordinate changes in the concentration and compartmentalization of syndecan-4 proteins. Specifically, syndecan-4 was lost from the dorsal aspect of the cell membrane and translocated from its intracellular pool to the ventral cell surface. Dissociation of syndecan-4 and vinculin from focal adhesions may contribute to promoting cell motility, because overexpression of syndecan-4, in part, blocked this dissociation and also retarded mechanical stretch-induced cell migration. These studies suggest that mechanical stress induces cell locomotion, in part, by the dynamic regulation of syndecan-4 expression and relocation.
Li
Lei
L
Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
Chaikof
Elliot L
EL
D000818:Animals; D015415:Biomarkers; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D053671:Syndecan-4; D014158:Transcription, Genetic; D016596:Vinculin / Q000378:metabolism
D015415:Biomarkers; D003470:Culture Media; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D016596:Vinculin