Uchil Pradeep D, Pawliczek Tobias, Reynolds Tracy D, Ding Siyuan, Hinz Angelika, Munro James B, Huang Fang, Floyd Robert W, Yang Haitao, Hamilton William L, Bewersdorf Joerg, Xiong Yong, Calderwood David A, Mothes Walther
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
J Cell Sci. 2014 Sep 15;127(Pt 18):3928-42. doi: 10.1242/jcs.143537. Epub 2014 Jul 11.
Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration.
粘着斑是将肌动蛋白细胞骨架与细胞外基质连接起来的大分子复合物。粘着斑的动态更新对于细胞迁移至关重要。桩蛋白是一种多接头蛋白，在调节粘着斑动态中起重要作用。在此，我们鉴定出TRIM15（一种三联基序蛋白家族成员）作为与桩蛋白相互作用的因子以及粘着斑的一个组分。TRIM15通过其卷曲螺旋结构域与桩蛋白的LD2基序之间的相互作用，以一种不依赖于肌球蛋白II的方式定位于粘着斑。与其他粘着斑蛋白不同，TRIM15是一种稳定的粘着斑组分，由于其形成寡聚体的能力而具有受限的流动性。除了粘着斑增大外，TRIM15缺失的细胞还表现出细胞迁移受损以及粘着斑解体速率降低。因此，我们的研究证明了TRIM15作为粘着斑更新和细胞迁移的调节组分的细胞功能。
