The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells.
The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells.
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DOI：
10.1042/bj20121701
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Mythreye K
中科院分区：
文献类型：
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作者：
Oh SY;Knelson EH;Blobe GC;Mythreye K
细胞的粘附和迁移受到肌动蛋白细胞骨架的调控变化的严格控制。先前我们报道了TGF-β超家族的辅助受体，III型TGF-β受体（t -β riii / β多糖），通过激活小GTPase、Cdc42和Cdc42依赖性的肌动蛋白细胞骨架改变，调节细胞粘附、迁移和侵袭，并部分抑制癌症进展。本研究表明，t - β riii特异性地促进MCF10A和HMEC乳腺上皮细胞丝状沟的形成和延伸。细胞表面t - β riii和Cdc42以β-arrestin2依赖和t - β ri / t - β rii独立的方式共定位于丝状结构和共络合物。β-arrestin2介导的t - β riii与Cdc42之间的相互作用增加了Cdc42效应物IRSp53与N-WASP之间的复合物形成，从而增加丝状线的形成。我们证明了丝状结构和上皮细胞粘附之间的功能联系是由TβRIII-Cdc42相互作用调节的。这些研究发现t - β riii是通过Cdc42调控IRSP53/NWASP的一种新型调节剂，可调节丝状面形成和细胞粘附。
Cell adhesion and migration are tightly controlled by regulated changes in the actin cytoskeleton. Previously we reported that the TGF-β superfamily coreceptor, the type III TGF-β receptor (TβRIII/betaglycan), regulates cell adhesion, migration and invasion and suppresses cancer progression in part, through activation of the small GTPase, Cdc42, and Cdc42-dependent alterations to the actin cytoskeleton. Here we demonstrate that TβRIII specifically promotes filopodial formation and extension in MCF10A and HMEC mammary epithelial cells. Mechanistically, cell surface TβRIII and Cdc42 colocalize to filopodial structures and co-complex in a β-arrestin2 dependent, and a TβRI/TβRII independent manner. The β-arrestin2-mediated interaction between TβRIII and Cdc42 increases complex formation between the Cdc42 effectors, IRSp53 with N-WASP, to increase filopodial formation. We demonstrate a function link between filopodial structures and epithelial cell adhesion as regulated by the TβRIII-Cdc42 interaction. These studies identify TβRIII as a novel regulator of IRSP53/NWASP via Cdc42 to regulate filopodial formation and cell adhesion.