title: Trans-regulation of Syndecan Functions by Hetero-oligomerization.
abstract: Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers. Biochemical and structural data revealed that recombinant syndecan-2 and -4 formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane domain mediated this interaction. When exogenously expressed in rat embryonic fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore, bimolecular fluorescence complementation-based assay demonstrated specific hetero-molecular interactions between syndecan-2 and -4, supporting hetero-oligomer formation of syndecans in vivo. Interestingly, hetero-oligomerization significantly reduced syndecan-4-mediated cellular processes such as protein kinase Cα activation and protein kinase Cα-mediated cell adhesion as well as syndecan-2-mediated tumorigenic activities in colon cancer cells such as migration and anchorage-independent growth. Taken together, these data provide evidence that hetero-oligomerization produces distinct syndecan functions and offer insights into the underlying signaling mechanisms of syndecans.
authors.affiliation: From the Department of Life Sciences, the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and.
authors.forename: Youngsil
authors.initials: Y
authors.lastname: Choi
authors.affiliation: From the Department of Life Sciences, the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and.
authors.forename: Mi-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: From the Department of Life Sciences, the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and.
authors.forename: Yangmi
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
authors.affiliation: From the Department of Life Sciences, the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and OhES@ewha.ac.kr.
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019281:Dimerization; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D053669:Syndecan-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053671:Syndecan-4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D053671:Syndecan-4; D053669:Syndecan-2
keywords: adhesion; cell migration; cell signaling; cell surface receptor; extracellular matrix; membrane; oligomerization; proteoglycan; receptor structure-function; syndecan