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XB-ART-44763
Cytoskeleton (Hoboken) March 1, 2012; 69 (3): 155-65.

Multiple domains of human CLASP contribute to microtubule dynamics and organization in vitro and in Xenopus egg extracts.

Patel K , Nogales E , Heald R .


Abstract
Cytoplasmic linker associated proteins (CLASPs) comprise a class of microtubule (MT) plus end-binding proteins (+TIPs) that contribute to the dynamics and organization of MTs during many cellular processes, among them mitosis. Human CLASP proteins contain multiple MT-binding domains, including tumor over-expressed gene (TOG) domains, and a Ser-x-Ile-Pro (SxIP) motif known to target some +TIPs though interaction with end-binding protein 1 (EB1). However, how individual domains contribute to CLASP function is poorly understood. We generated full-length recombinant human CLASP1 and a series of truncation mutants and found that two N-terminal TOG domains make the strongest contribution to MT polymerization and bundling, but also identified a third TOG domain that further contributes to CLASP activity. Plus end tracking by CLASP requires the SxIP motif and interaction with EB1. The C-terminal coiled-coil domain mediates dimerization and association with many other factors, including the kinetochore motor centromere protein E (CENP-E), and the chromokinesin Xkid. Only the full-length protein was able to rescue spindle assembly in Xenopus egg extracts depleted of endogenous CLASP. Deletion of the C-terminal domain caused aberrant MT polymerization and dramatic spindle phenotypes, even with small amounts of added protein, indicating that proper localization of CLASP activity is essential to control MT polymerization during mitosis.

PubMed ID: 22278908
PMC ID: PMC3315288
Article link: Cytoskeleton (Hoboken)
Grant support: [+]
Genes referenced: bag3 cenpe ckap5 clasp1 clip1 kif22 mapre1 prc1


Article Images: [+] show captions
References [+] :
Al-Bassam, CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule. 2010, Pubmed


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