Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage

Daniela Triolo, Giorgia Dina, Isabella Lorenzetti, Maria Chiara Malaguti, Paolo Morana, Ubaldo Del Carro, Giancarlo Comi, Albee Messing, Angelo Quattrini, Stefano C. Previtali

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Axonal loss causes disabling and permanent deficits in many peripheral neuropathies, and may result from inefficient nerve regeneration due to a defective relationship between Schwann cells, axons and the extracellular matrix. These interactions are mediated by surface receptors and transduced by cytoskeletal molecules. We investigated whether peripheral nerve regeneration is perturbed in mice that lack glial fibrillary acidic protein (GFAP), a Schwann-cell-specific cytoskeleton constituent upregulated after damage. Peripheral nerves develop and function normally in GFAP-null mice. However, axonal regeneration after damage was delayed. Mutant Schwann cells maintained the ability to dedifferentiate but showed defective proliferation, a key event for successful nerve regeneration. We also showed that GFAP and the other Schwann-cell-intermediate filament vimentin physically interact in two distinct signaling pathways involved in proliferation and nerve regeneration. GFAP binds integrin αvβ8, which initiates mitotic signals soon after damage by interacting with fibrin. Consistently, ERK phosphorylation was reduced in crushed GFAP-null nerves. Vimentin instead binds integrin α5β1, which regulates proliferation and differentiation later in regeneration, and may compensate for the absence of GFAP in mutant mice. GFAP might contribute to form macro-complexes to initiate mitogenic and differentiating signaling for efficient nerve regeneration.

Original languageEnglish
Pages (from-to)3981-3993
Number of pages13
JournalJournal of Cell Science
Volume119
Issue number19
DOIs
Publication statusPublished - Oct 1 2006

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Nerve Regeneration
Schwann Cells
Glial Fibrillary Acidic Protein
Cell Proliferation
Vimentin
Peripheral Nerves
Integrins
Regeneration
Intermediate Filaments
Peripheral Nervous System Diseases
Fibrin
Cytoskeleton
Extracellular Matrix
Axons
Phosphorylation

Keywords

  • Adhesion
  • Cytoskeleton
  • Extracellular matrix
  • Nerve regeneration
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology

Cite this

Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. / Triolo, Daniela; Dina, Giorgia; Lorenzetti, Isabella; Malaguti, Maria Chiara; Morana, Paolo; Del Carro, Ubaldo; Comi, Giancarlo; Messing, Albee; Quattrini, Angelo; Previtali, Stefano C.

In: Journal of Cell Science, Vol. 119, No. 19, 01.10.2006, p. 3981-3993.

Research output: Contribution to journalArticle

Triolo, Daniela ; Dina, Giorgia ; Lorenzetti, Isabella ; Malaguti, Maria Chiara ; Morana, Paolo ; Del Carro, Ubaldo ; Comi, Giancarlo ; Messing, Albee ; Quattrini, Angelo ; Previtali, Stefano C. / Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. In: Journal of Cell Science. 2006 ; Vol. 119, No. 19. pp. 3981-3993.
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