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Dev Cell. 2015 Oct 26;35(2):186-98. doi: 10.1016/j.devcel.2015.09.018.

Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by Linking the Nuclear Envelope to the Actin and Microtubule Cytoskeleton.

Author information

1
IGBMC, INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France; University Claude Bernard Lyon 1, CGphiMC UMR CNRS 5534, 69622 Villeurbanne, France. Electronic address: manuela.dalessandro2@gmail.com.
2
IGBMC, INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France.
3
Myology Group, UMR S 787 INSERM, Université Pierre et Marie Curie Paris 6, 75634 Paris, France; CNRS UMR5239, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
4
Morphology Neuromuscular Unit of the Myology Institute, GHU Pitié-Salpêtrière, 75013 Paris, France.
5
IGBMC, INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France; Cell Biology and Biophysics Unit, EMBL Heidelberg, 69117 Heidelberg, Germany.
6
Myology Group, UMR S 787 INSERM, Université Pierre et Marie Curie Paris 6, 75634 Paris, France; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
7
IGBMC, INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France; UMR7622, IBPS, UPMC, 75252 Paris, France.
8
IGBMC, INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France. Electronic address: jocelyn@igbmc.fr.

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.

PMID:
26506308
DOI:
10.1016/j.devcel.2015.09.018
[Indexed for MEDLINE]
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