RRC ID 45548
Author D'Alessandro M, Hnia K, Gache V, Koch C, Gavriilidis C, Rodriguez D, Nicot AS, Romero NB, Schwab Y, Gomes E, Labouesse M, Laporte J.
Title Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by Linking the Nuclear Envelope to the Actin and Microtubule Cytoskeleton.
Journal Dev Cell
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.
Volume 35(2)
Pages 186-98
Published 2015-10-26
DOI 10.1016/j.devcel.2015.09.018
PII S1534-5807(15)00619-X
PMID 26506308
MeSH Actins / genetics Animals COS Cells Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Cell Nucleus / genetics* Cell Shape / genetics Chlorocebus aethiops Cytoplasm / metabolism Cytoskeleton / genetics Cytoskeleton / metabolism Cytoskeleton / pathology HEK293 Cells Humans Microfilament Proteins / genetics* Microfilament Proteins / metabolism Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism Microtubules / genetics Microtubules / metabolism Multiprotein Complexes Muscle, Skeletal / metabolism Myopathies, Structural, Congenital / genetics* Myopathies, Structural, Congenital / metabolism Myopathies, Structural, Congenital / pathology Neoplasm Proteins / genetics* Neoplasm Proteins / metabolism Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Nuclear Envelope / genetics* Nuclear Envelope / metabolism Nuclear Proteins / genetics* Nuclear Proteins / metabolism
IF 10.092
Times Cited 30
C.elegans tm1060