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Hierarchy between the transmembrane and cytoplasmic domains in the regulation of syndecan-4 functions

Title
Hierarchy between the transmembrane and cytoplasmic domains in the regulation of syndecan-4 functions
Authors
Choi Y.Kang D.Han I.-O.Oh E.-S.
Ewha Authors
오억수강동민
SCOPUS Author ID
오억수scopus; 강동민scopus
Issue Date
2012
Journal Title
Cellular Signalling
ISSN
0898-6568JCR Link
Citation
vol. 24, no. 8, pp. 1522 - 1530
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Syndecan-4, a transmembrane heparan sulfate proteoglycan, plays a critical role in cell adhesion. Both the transmembrane and cytoplasmic domains of syndecan-4 are known to contribute to its functions, but the regulatory mechanisms underlying the functional interplay between the two domains were previously unclear. Here, we examined the functional relationship between these two domains. Fluorescence resonance energy transfer (FRET)-based assays showed that syndecan-4 expression enhanced RhoA activation. Furthermore, rat embryonic fibroblasts (REFs) plated on fibronectin fragments lacking the heparin-binding domain that interacts with syndecan-4 showed much lower RhoA activation than that in cells plated on full-length fibronectin, indicating that RhoA is involved in syndecan-4-mediated cell adhesion signaling. Syndecan-4 mutants defective in transmembrane domain-induced oligomerization and syndecan-4 phosphorylation-mimicking cytoplasmic domain mutants showed decreases in RhoA activation and RhoA-related functions, such as adhesion, spreading and focal adhesion formation, and subsequent increase in cell migration, but the inhibitory effect was much higher in cells expressing the transmembrane domain mutants. The cytoplasmic domain mutants (but not the transmembrane domain mutants) retained the capacity to form SDS-resistant dimers, and the cytoplasmic mutants showed less inhibition of syndecan-4-mediated protein kinase C activation compared to the transmembrane domain mutants. Finally, cytoplasmic domain activation failed to overcome the inhibition conferred by mutation of the transmembrane domain. Taken together, these data suggest that the transmembrane domain plays a major role in regulating syndecan-4 functions, and further show that a domain hierarchy exists in the regulation of syndecan-4. © 2012 Elsevier Inc.
DOI
10.1016/j.cellsig.2012.03.020
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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