RRC ID |
45548
|
著者 |
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.
|
タイトル |
Amphiphysin 2 Orchestrates Nucleus Positioning and Shape by Linking the Nuclear Envelope to the Actin and Microtubule Cytoskeleton.
|
ジャーナル |
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.
|
巻・号 |
35(2)
|
ページ |
186-98
|
公開日 |
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
|
引用数 |
30
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
リソース情報 |
線虫 |
tm1060 |