Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells
| Autor: | Radoslaw M. Sobota, Rutti Patel, Victoria Koullourou, Kamel Mamchaoui, Bruno Cadot, Brian Burke, Yin Loon Lee, François Nédélec, Jan Schmoranzer, Sue Shackleton, Edgar R. Gomes, Alessandra Calvi, Petra Gimpel |
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| Přispěvatelé: | HAL-UPMC, Gestionnaire, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nuclear Envelope nuclear positioning A Kinase Anchor Proteins Nerve Tissue Proteins Biology Microtubules Article General Biochemistry Genetics and Molecular Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine PCM1 Microtubule [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology cytosim computer simulation skeletal muscle Cytoskeleton Microtubule nucleation Cell Nucleus Centrosome Nesprin Akap450 Nuclear Proteins Biological Transport Microtubule organizing center Nesprin-1α Rats Cell biology Cytoskeletal Proteins 030104 developmental biology non-centrosomal MTOC Kinesin Nesprin-1 Female General Agricultural and Biological Sciences Microtubule-Associated Proteins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Current Biology-CB Current Biology-CB, 2017, ⟨10.1016/j.cub.2017.08.031⟩ Current Biology Current Biology-CB, Elsevier, 2017, ⟨10.1016/j.cub.2017.08.031⟩ |
| ISSN: | 0960-9822 1879-0445 |
| Popis: | Summary The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to the accumulation of centrosomal proteins and microtubule (MT) nucleation activity at the nuclear envelope (NE) [1, 2, 3, 4]. The relocalization of centrosomal proteins, including Pericentrin, Pcm1, and γ-tubulin, depends on Nesprin-1, an outer nuclear membrane (ONM) protein that connects the nucleus to the cytoskeleton via its N-terminal region [5, 6, 7]. Nesprins are also involved in the recruitment of kinesin to the NE and play a role in nuclear positioning in skeletal muscle cells [8, 9, 10, 11, 12]. However, a function for MT nucleation from the NE in nuclear positioning has not been established. Using the proximity-dependent biotin identification (BioID) method [13, 14], we found several centrosomal proteins, including Akap450, Pcm1, and Pericentrin, whose association with Nesprin-1α is increased in differentiated myotubes. We show that Nesprin-1α recruits Akap450 to the NE independently of kinesin and that Akap450, but not other centrosomal proteins, is required for MT nucleation from the NE. Furthermore, we demonstrate that this mechanism is disrupted in congenital muscular dystrophy patient myotubes carrying a nonsense mutation within the SYNE1 gene (23560 G>T) encoding Nesprin-1 [15, 16]. Finally, using computer simulation and cell culture systems, we provide evidence for a role of MT nucleation from the NE on nuclear spreading in myotubes. Our data thus reveal a novel function for Nesprin-1α/Nesprin-1 in nuclear positioning through recruitment of Akap450-mediated MT nucleation activity to the NE. Graphical Abstract Highlights • BioID of Nesprin-1α identifies centrosomal proteins at myotube nuclear envelope • Nesprin-1α-containing LINC complexes recruit Akap450 to myotube nuclear envelope • Akap450 is required for microtubule nucleation at the nuclear envelope • Microtubule nucleation at the nuclear envelope is involved in nuclear positioning Gimpel et al. find that LINC complexes comprising Nesprin-1α and Sun1/2 are required for the recruitment of centrosomal proteins and Akap450-mediated microtubule nucleation activity to the myotube nuclear envelope. Absence of microtubule nucleation from the nucleus affects nuclear positioning in muscle cells in vitro and in computer simulations. |
| Databáze: | OpenAIRE |
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