Logo image
Back
Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex
Journal article   Open access   Peer reviewed

Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex

Jonathan H Hecht, Joshua A Weiner, Steven R Post and Jerold Chun
The Journal of cell biology, Vol.135(4), pp.1071-1083
11/1996
DOI: 10.1083/jcb.135.4.1071
PMCID: PMC2133395
PMID: 8922387
url
https://doi.org/10.1083/jcb.135.4.1071View
Published (Version of record) Open Access

Abstract

Neocortical neuroblast cell lines were used to clone G-protein-coupled receptor (GPCR) genes to study signaling mechanisms regulating cortical neurogenesis. One putative GPCR gene displayed an in situ expression pattern enriched in cortical neurogenic regions and was therefore named ventricular zone gene-1 (vzg-1). The vzg-1 cDNA hybridized to a 3.8-kb mRNA transcript and encoded a protein with a predicted molecular mass of 41-42 kD, confirmed by Western blot analysis. To assess its function, vzg-1 was overexpressed in a cell line from which it was cloned, inducing serum-dependent "cell rounding." Lysophosphatidic acid (LPA), a bioactive lipid present in high concentrations in serum, reproduced the effect seen with serum alone. Morphological responses to other related phospholipids or to thrombin, another agent that induces cell rounding through a GPCR, were not observed in vzg-1 overexpressing cells. Vzg-1 overexpression decreased the EC50 of both cell rounding and Gi activation in response to LPA. Pertussis toxin treatment inhibited vzg-1-dependent LPA-mediated Gi activation, but had no effect on cell rounding. Membrane binding studies indicated that vzg-1 overexpression increased specific LPA binding. These analyses identify the vzg-1 gene product as a receptor for LPA, suggesting the operation of LPA signaling mechanisms in cortical neurogenesis. Vzg-1 therefore provides a link between extracellular LPA and the activation of LPA-mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems.
 Pregnancy Transfection Lysophospholipids - metabolism Age Factors Molecular Sequence Data Neurons - cytology Embryo, Mammalian - chemistry Cerebral Cortex - cytology Dose-Response Relationship, Drug Base Sequence Lysophospholipids - pharmacology Female Neurons - drug effects Gene Expression Regulation, Developmental - physiology Receptors, Lysophosphatidic Acid Cerebral Cortex - chemistry Amino Acid Sequence GTP-Binding Proteins - physiology Neurons - chemistry Membrane Proteins - genetics Cell Size - drug effects Receptors, G-Protein-Coupled Cell Line - chemistry Animals Cerebral Cortex - embryology Signal Transduction - physiology Mice Mice, Inbred BALB C Receptors, Cell Surface - genetics

Details

Metrics

26 Record Views
665 Times Cited - Web of Science
Logo image