English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Profilin 1 is required for peripheral nervous system myelination

Montani, L., Buerki-Thurnherr, T., de Faria, J. P., Pereira, J. A., Dias, N. G., Fernandes, R., et al. (2014). Profilin 1 is required for peripheral nervous system myelination. DEVELOPMENT, 141(7), 1553-1561. doi:10.1242/dev.101840.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Montani, Laura1, Author
Buerki-Thurnherr, Tina1, Author
de Faria, Joana Paes1, Author
Pereira, Jorge A.1, Author
Dias, Nuno G.1, Author
Fernandes, Rui1, Author
Goncalves, Ana F.1, Author
Braun, Attila2, Author              
Benninger, Yves1, Author
Böttcher, Ralph T.2, Author              
Costell, Mercedes2, Author              
Nave, Klaus-Armin1, Author
Franklin, Robin J. M.1, Author
Meijer, Dies1, Author
Suter, Ueli1, Author
Relvas, Joao B.1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

Content

show
hide
Free keywords: SCHWANN-CELLS; N-WASP; TYROSINE KINASE; BETA-1-INTEGRIN; RAC1; DIFFERENTIATION; MIGRATION; GROWTH; CDC42; AXONSProfilin; Myelination; Schwann cell; Mouse;
 Abstract: Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization. Pfn1 is inhibited upon phosphorylation by ROCK, a downstream effector of the integrin-linked kinase pathway. Thus, a dramatic reduction of radial lamellipodia formation is observed in SCs lacking integrin-linked kinase or treated with the Rho/ROCK activator lysophosphatidic acid. Knocking down Pfn1 expression by lentiviral-mediated shRNA delivery impairs SC lamellipodia formation in vitro, suggesting a direct role for this protein in PNS myelination. Indeed, SC-specific gene ablation of Pfn1 in mice led to profound radial sorting and myelination defects, confirming a central role for this protein in PNS development. Our data identify Pfn1 as a key effector of the integrin linked kinase/Rho/ROCK pathway. This pathway, acting in parallel with integrin beta 1/LCK/Rac1 and their effectors critically regulates SC lamellipodia formation, radial sorting and myelination during peripheral nervous system maturation.

Details

show
hide
Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000333184500014
DOI: 10.1242/dev.101840
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: DEVELOPMENT
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND : COMPANY OF BIOLOGISTS LTD
Pages: - Volume / Issue: 141 (7) Sequence Number: - Start / End Page: 1553 - 1561 Identifier: ISSN: 0950-1991