Profilin 1 is required for peripheral nervous system myelination
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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

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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.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.rights.uri info:eu-repo/semantics/openAccess
dc.source 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.subject Biotecnologia
dc.subject Cèl·lules
dc.subject Proteïnes
dc.title Profilin 1 is required for peripheral nervous system myelination
dc.type info:eu-repo/semantics/article
dc.date.updated 2016-06-08T13:14:58Z
dc.identifier.doi http://dx.doi.org/10.1242/dev.101840
dc.identifier.idgrec 111997

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