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Profilin 1 is required for peripheral nervous system myelination

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Profilin 1 is required for peripheral nervous system myelination

dc.contributor.author	Montani, Laura
dc.contributor.author	Buerki-Thurnherr, Tina
dc.contributor.author	Paes de Faria, Joana
dc.contributor.author	Pereira, Jorge A.
dc.contributor.author	Dias, Nuno G.
dc.contributor.author	Fernandes, Rui
dc.contributor.author	Gonçalves, Ana F.
dc.contributor.author	Braun, Attila
dc.contributor.author	Benninger, Yves
dc.contributor.author	Böttcher, Ralph T.
dc.contributor.author	Costell Rosselló, Mercedes
dc.contributor.author	Nave, Klaus-Armin
dc.contributor.author	Franklin, Robin J. M.
dc.contributor.author	Meijer, Dies
dc.contributor.author	Suter, Ueli
dc.contributor.author	Relvas, João B.
dc.date.accessioned	2016-06-08T13:14:57Z
dc.date.available	2016-06-08T13:14:57Z
dc.date.issued	2014
dc.identifier.citation	Montani, Laura Buerki-Thurnherr, Tina Paes de Faria, Joana Pereira, Jorge A. Dias, Nuno G. Fernandes, Rui Gonçalves, Ana F. Braun, Attila Benninger, Yves Böttcher, Ralph T. Costell Rosello, Mercedes Nave, Klaus-Armin Franklin, Robin J. M. Meijer, Dies Suter, Ueli Relvas, João B. 2014 Profilin 1 is required for peripheral nervous system myelination Development 141 1553 1561
dc.identifier.uri	http://hdl.handle.net/10550/53991
dc.description.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 actinbinding 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 integrinlinked kinase or treated with the Rho/ROCK activator lysophosphatidic acid. Knocking down Pfn1 expression by lentiviralmediated 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 β1/LCK/Rac1 and their effectors critically regulates SC lamellipodia formation, radial sorting and myelination during peripheral nervous system maturation.
dc.language.iso	eng
dc.relation.ispartof	Development, 2014, vol. 141, p. 1553-1561
dc.subject	Biotecnologia
dc.subject	Cèl·lules
dc.subject	Proteïnes
dc.title	Profilin 1 is required for peripheral nervous system myelination
dc.type	journal article	es_ES
dc.date.updated	2016-06-08T13:14:58Z
dc.identifier.doi	10.1242/dev.101840
dc.identifier.idgrec	111997
dc.rights.accessRights	open access	es_ES