Granés F, García R, Casaroli-Marano R P, Castel S, Rocamora N, Reina M, Ureña J M, Vilaró S
Department of Cell Biology, University of Barcelona, Diagonal 645, Barcelona, 08028, Spain.
Exp Cell Res. 1999 May 1;248(2):439-56. doi: 10.1006/excr.1999.4437.
The syndecans, a family of transmembrane heparan sulfate proteoglycans, are ubiquitous molecules whose intracellular function is still unknown. To examine the function of syndecan-2, one of the most abundant heparan sulfate proteoglycan in fibroblasts, we performed transfection studies in COS-1 and Swiss 3T3 cells. Endogenous syndecan-2 colocalized with F-actin in cortical structures. Overexpression of full-length syndecan-2 induced the formation of long filopodia-like structures. These changes correlated with a rearrangement of the actin cytoskeleton, which strongly colocalized with syndecan-2. Overexpression of syndecan-2 lacking the extracellular domain increased the number of microspikes on the cell surface but failed to induce filopodia. Addition of heparin blocked the effect of full-length syndecan-2, suggesting that heparan sulfate chains in the extracellular domain are necessary to induce filopodia. Coexpression of cdc42Hs negative-dominant N17 blocked syndecan-2-induced filopodia and cdc42Hs positive-dominant V12 had a synergic effect. This indicates that active cdc42Hs is necessary for syndecan-2 induction of filopodia. These results provide a link between syndecan-2, actin cytoskeleton, and cdc42Hs.
Syndecans是一类跨膜硫酸乙酰肝素蛋白聚糖家族，是普遍存在的分子，但其细胞内功能尚不清楚。为了研究Syndecan-2（成纤维细胞中最丰富的硫酸乙酰肝素蛋白聚糖之一）的功能，我们在COS-1和瑞士3T3细胞中进行了转染研究。内源性Syndecan-2与F-肌动蛋白在皮质结构中共定位。全长Syndecan-2的过表达诱导了长丝状伪足样结构的形成。这些变化与肌动蛋白细胞骨架的重排相关，肌动蛋白细胞骨架与Syndecan-2强烈共定位。缺乏细胞外结构域的Syndecan-2的过表达增加了细胞表面微刺的数量，但未能诱导丝状伪足的形成。添加肝素可阻断全长Syndecan-2的作用，表明细胞外结构域中的硫酸乙酰肝素链是诱导丝状伪足所必需的。cdc42Hs负显性N17的共表达阻断了Syndecan-2诱导的丝状伪足，而cdc42Hs正显性V12具有协同作用。这表明活性cdc42Hs是Syndecan-2诱导丝状伪足所必需的。这些结果在Syndecan-2、肌动蛋白细胞骨架和cdc42Hs之间建立了联系。
