Profilin 1 is required for peripheral nervous system myelination

Laura Montani, Tina Buerki-Thurnherr, Joana Paes de Faria, Jorge A Pereira, Nuno G Dias, Rui Fernandes, Ana F Gonçalves, Attila Braun, Yves Benninger, Ralph T Böttcher, Mercedes Costell, Klaus-Armin Nave, Robin J M Franklin, Dies Meijer, Ueli Suter, João B Relvas

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 β1/LCK/Rac1 and their effectors critically regulates SC lamellipodia formation, radial sorting and myelination during peripheral nervous system maturation.

Original languageEnglish
Pages (from-to)1553-61
Number of pages9
Issue number7
Publication statusPublished - Apr 2014

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Axonal Transport
  • Cells, Cultured
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Sheath
  • Neurogenesis
  • Neuropeptides
  • Peripheral Nerves
  • Peripheral Nervous System
  • Profilins
  • Pseudopodia
  • Schwann Cells
  • rac1 GTP-Binding Protein


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