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Nat Cell Biol. 2014 Jun;16(6):561-73. doi: 10.1038/ncb2975. Epub 2014 May 25.

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

Author information

1
1] Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue San Francisco, California 94143, USA [2].
2
1] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California San Francisco, 513 Parnassus Avenue San Francisco, California 94143, USA [2].
3
Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue San Francisco, California 94143, USA.

Abstract

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 (also known as PHLDB2), which recruits CLASPs to FAs, facilitate FA disassembly. CLASPs are further required for FA-associated ECM degradation, and matrix metalloprotease inhibition slows FA disassembly similarly to CLASP or PHLDB2 (LL5β) depletion. Finally, CLASP-mediated microtubule tethering at FAs establishes an 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.

PMID:
24859005
PMCID:
PMC4108447
DOI:
10.1038/ncb2975
[Indexed for MEDLINE]
Free PMC Article

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