Journal article
Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid
Proceedings of the National Academy of Sciences - PNAS, Vol.96(9), pp.5233-5238
04/27/1999
DOI: 10.1073/pnas.96.9.5233
PMCID: PMC21847
PMID: 10220449
Abstract
Lysophosphatidic acid (LPA) is a bioactive phospholipid with properties of an extracellular growth factor for many cell lines, including those derived from neuroblastomas. However, the relevance of LPA signaling to the normal, developing nervous system is unknown, in part reflecting the previous unavailability of cloned receptor genes. Recent studies of the first such gene, encoding the G protein-coupled receptor LP
A1
/VZG-1 (lysophospholipid receptor A1/ventricular zone gene-1), revealed a major locus of expression in oligodendrocytes and Schwann cells (SCs) during development, suggesting an influence of LPA on these myelinating cells. Here we report that LPA (≥10 nM) is a potent survival factor for cultured neonatal SCs, with survival activity equaling the maximal effect of neuregulin, the major peptide SC survival factor. LPA activates a pharmacologically defined signaling pathway in SCs, involving G
i
and phosphoinositide 3-kinase. Moreover, LPA’s effect depends on Akt, a downstream kinase that can mediate phosphoinositide 3-kinase-dependent survival, as demonstrated by both Western blot and transfection analyses. Overexpression of functional epitope-tagged LP
A1
/VZG-1 protein decreases SC apoptosis in response to serum withdrawal. These data demonstrate a role for extracellular LPA and its receptor LP
A1
/VZG-1 in SC survival and, more broadly, implicate G protein-coupled receptor-mediated lysophospholipid signaling as a significant mechanism in neural development.
Details
- Title: Subtitle
- Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid
- Creators
- Joshua A Weiner - Graduate Programs in Neurosciences and Biomedical Sciences, The Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636Jerold Chun - Graduate Programs in Neurosciences and Biomedical Sciences, The Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.96(9), pp.5233-5238
- DOI
- 10.1073/pnas.96.9.5233
- PMID
- 10220449
- PMCID
- PMC21847
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- The National Academy of Sciences
- Language
- English
- Date published
- 04/27/1999
- Academic Unit
- Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983997989102771
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