| Literature DB >> 26506308 |
Manuela D'Alessandro1, Karim Hnia2, Vincent Gache3, Catherine Koch2, Christos Gavriilidis2, David Rodriguez2, Anne-Sophie Nicot2, Norma B Romero4, Yannick Schwab5, Edgar Gomes6, Michel Labouesse7, Jocelyn Laporte8.
Abstract
Nucleus positioning is key for intracellular organization, cell differentiation, and organ development and is affected in many diseases, including myopathies due to alteration in amphiphysin-2 (BIN1). The actin and microtubule cytoskeletons are essential for nucleus positioning, but their crosstalk in this process is sparsely characterized. Here, we report that impairment of amphiphysin/BIN1 in Caenorhabditis elegans, mammalian cells, or muscles from patients with centronuclear myopathy alters nuclear position and shape. We show that AMPH-1/BIN1 binds to nesprin and actin, as well as to the microtubule-binding protein CLIP170 in both species. Expression of the microtubule-anchoring CAP-GLY domain of CLIP170 fused to the nuclear-envelope-anchoring KASH domain of nesprin rescues nuclear positioning defects of amph-1 mutants. Amphiphysins thus play a central role in linking the nuclear envelope with the actin and microtubule cytoskeletons. We propose that BIN1 has a direct and evolutionarily conserved role in nuclear positioning, altered in myopathies.Entities:
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Year: 2015 PMID： 26506308 DOI： 10.1016/j.devcel.2015.09.018
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270