Signal transduction pathways implicated in neural recognition molecule L1 triggered neuroprotection and neuritogenesis

Gabriele Loers, Suzhen Chen, Martin Grumet, Melitta Camartin

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The signal transduction pathways involved in adhesion molecule L1-triggered neuritogenesis and neuroprotection were investigated using the extracellular domain of mouse or human L1 in fusion with the Fc portion of human immunoglobutin G or L1 purified from mouse brain by affinity chromatography. Substrate L1-triggered neuritogenesis and neuroprotection depended on distinct but also overlapping signal transduction pathways and on the expression of L1 at the neuronal cell surface. PI3 kinase inhibitors, Src family kinase inhibitors as well as mitogen-activated protein kinase kinase inhibitors reduced both L1-triggered neuritogenesis and neuroprotection. In contrast, fibroblast growth factor receptor inhibitors, a protein kinase A inhibitor, and an inhibitor of cAMP-mediated signal transduction pathways, blocked neuritogenesis, but did not affect L1-triggered neuroprotection. Proteolytic cleavage of L1 or its interaction partners is necessary for both L1-mediated neuritogensis and neuroprotection. Furthermore, L1-triggered neuroprotection was found to be associated with increased phosphorylation of extracellular signal-regulated kinases 1/2, Akt and Bad, and inhibition of caspases. These observations suggest possibilities of differentially targeting signal transduction pathways for L1-dependent neuritogenesis and neuroprotection.

Original languageEnglish (US)
Pages (from-to)1463-1476
Number of pages14
JournalJournal of neurochemistry
Volume92
Issue number6
DOIs
StatePublished - Mar 1 2005

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Signal transduction
Signal Transduction
Molecules
Affinity chromatography
Fibroblast Growth Factor Receptors
Phosphorylation
Mitogen-Activated Protein Kinase 3
src-Family Kinases
Mitogen-Activated Protein Kinase Kinases
Caspases
Cyclic AMP-Dependent Protein Kinases
Phosphatidylinositol 3-Kinases
Brain
Fusion reactions
Adhesion
Mitogen-Activated Protein Kinase 1
Protein Kinase Inhibitors
Neuroprotection
Affinity Chromatography
Substrates

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Biochemistry

Keywords

  • FGF receptor
  • MAP kinase
  • Neural cell adhesion molecule L1
  • Neuritogenesis
  • Neuroprotection
  • Proteolytic cleavage

Cite this

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Signal transduction pathways implicated in neural recognition molecule L1 triggered neuroprotection and neuritogenesis. / Loers, Gabriele; Chen, Suzhen; Grumet, Martin; Camartin, Melitta.

In: Journal of neurochemistry, Vol. 92, No. 6, 01.03.2005, p. 1463-1476.

Research output: Contribution to journalArticle

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