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Publication : Kindlin1 regulates microtubule function to ensure normal mitosis.

First Author  Patel H Year  2016
Journal  J Mol Cell Biol Volume  8
Issue  4 Pages  338-48
PubMed ID  26993041 Mgi Jnum  J:317585
Mgi Id  MGI:6843977 Doi  10.1093/jmcb/mjw009
Citation  Patel H, et al. (2016) Kindlin1 regulates microtubule function to ensure normal mitosis. J Mol Cell Biol 8(4):338-48
abstractText  Loss of Kindlin 1 (Kin1) results in the skin blistering disorder Kindler Syndrome (KS), whose symptoms also include skin atrophy and reduced keratinocyte proliferation. Kin1 binds to integrins to modulate their activation and more recently it has been shown to regulate mitotic spindles and cell survival in a Plk1-dependent manner. Here we report that short-term Kin1 deletion in mouse skin results in impaired mitosis, which is associated with reduced acetylated tubulin (ac-tub) levels and cell proliferation. In cells, impaired mitosis and reduced ac-tub levels are also accompanied by reduced microtubule stability, all of which are rescued by HDAC6 inhibition. The ability of Kin1 to regulate HDAC6-dependent cellular ac-tub levels is dependent on its phosphorylation by Plk1. Taken together, these data define a novel role for Kin1 in microtubule acetylation and stability and offer a mechanistic insight into how certain KS phenotypes, such as skin atrophy and reduced cell proliferation, arise.
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