CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis and adhesion site turnover.

CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis and adhesion site turnover.
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DOI:
10.1038/ncb2975
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发表时间:
2014-06
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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--
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整合素为基础的局灶黏附(FAs)与细胞外基质(ECM)的转换是协调细胞运动所必需的。在集体迁移的人角质形成细胞中,FAs聚集在前缘附近,由于收缩力而生长和成熟,并在前进的细胞体下分解。我们报道,微管相关的CLASP1和CLASP2蛋白聚集在FAs周围与FA周转有时间相关性。class和LL5β(将class招募到FAs)促进FA的分解。FA相关的ECM降解进一步需要CLASPs,基质金属蛋白酶抑制减缓FA分解,类似于CLASP或LL5β耗竭。最后,clasp介导的FAs微管系聚建立了一个fa导向的转运途径,用于FAs附近的胞外囊泡的递送、对接和局部融合。我们认为,CLASPs结合了微管组织、囊泡运输和细胞与ECM的相互作用,建立了一个局部分泌途径,通过切断细胞-基质连接促进FA的周转。
Turnover of integrin-based focal adhesions (FAs) with the extracellular matrix (ECM) is essential for coordinated cell movement. In collectively migrating human keratinocytes, FAs assemble near the leading edge, grow and mature as a result of contractile forces, and disassemble underneath the advancing cell body. We report that clustering of microtubule-associated CLASP1 and CLASP2 proteins around FAs temporally correlates with FA turnover. CLASPs and LL5β, which recruits CLASPs to FAs, facilitate FA disassembly. CLASPs are further required for FA-associated ECM degradation, and matrix metalloprotease inhibition slows FA disassembly similar to CLASP or LL5β depletion. Finally, CLASP-mediated microtubuletethering at FAs establishes a FA-directed transport pathway for delivery, docking and localized fusion of exocytic vesicles near FAs. We propose that CLASPs couple microtubule organization, vesicle transport and cell interactions with the ECM, establishing a local secretion pathway that facilitates FA turnover by severing cell-matrix connections.
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