Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 22, Issue 1, Pages 61-68Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hq0102.100314
Keywords
restenosis; hypertension; atherosclerosis; heparan sulfate; syndecan
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Funding
- NHLBI NIH HHS [R01HL60903] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL060903] Funding Source: NIH RePORTER
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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 tray 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.
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