Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells - Sorbonne Université Access content directly
Journal Articles Current Biology - CB Year : 2017

Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells

Yin Loon Loon Lee
  • Function : Author
Radoslaw M. M Sobota
  • Function : Author
Brian Burke
  • Function : Author
Alessandra Calvi
  • Function : Author
Victoria Koullourou
  • Function : Author
Rutti Patel
  • Function : Author
François Nédélec
  • Function : Author
Sue Shackleton
  • Function : Author
Jan Schmoranzer
  • Function : Author
Edgar R. Gomes
  • Function : Author
  • PersonId : 983623

Abstract

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.
Fichier principal
Vignette du fichier
1-s2.0-S0960982217310692-main.pdf (6.5 Mo) Télécharger le fichier
Origin Publication funded by an institution
Loading...

Dates and versions

hal-01598133 , version 1 (29-09-2017)

Licence

Identifiers

Cite

Petra Gimpel, Yin Loon Loon Lee, Radoslaw M. M Sobota, Brian Burke, Alessandra Calvi, et al.. Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells. Current Biology - CB, 2017, ⟨10.1016/j.cub.2017.08.031⟩. ⟨hal-01598133⟩
862 View
432 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More