Cited by 291Neurogenesis and neuroplasticity mechanismsFetal and Pediatric Neurological DisordersGenetics and Neurodevelopmental Disorders

G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination

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Luo, Rong, Jeong, Sung-Jin, Jin, Zhaohui, Strokes, Natalie, Li, Shihong, Piao, Xianhua·2011·Proceedings of the National Academy of Sciences

Abstract

GPR56, an orphan G protein-coupled receptor (GPCR) from the family of adhesion GPCRs, plays an indispensable role in cortical development and lamination. Mutations in the GPR56 gene cause a malformed cerebral cortex in both humans and mice that resembles cobblestone lissencephaly, which is characterized by overmigration of neurons beyond the pial basement membrane. However, the molecular mechanisms through which GPR56 regulates cortical development remain elusive due to the unknown status of its ligand. Here we identify collagen, type III, alpha-1 (gene symbol Col3a1 ) as the ligand of GPR56 through an in vitro biotinylation/proteomics approach. Further studies demonstrated that Col3a1 null mutant mice exhibit overmigration of neurons beyond the pial basement membrane and a cobblestone-like cortical malformation similar to the phenotype seen in Gpr56 null mutant mice. Functional studies suggest that the interaction of collagen III with its receptor GPR56 inhibits neural migration in vitro. As for intracellular signaling, GPR56 couples to the Gα 12/13 family of G proteins and activates RhoA pathway upon ligand binding. Thus, collagen III regulates the proper lamination of the cerebral cortex by acting as the major ligand of GPR56 in the developing brain.

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Authors
Luo, R., Jeong, S.-J., Jin, Z., Strokes, N., Li, S., & Piao, X.
Affiliations
Boston Children's Hospital (US)
Venue
Proceedings of the National Academy of Sciences
Published
2011-07-18
Volume
108
Issue
31
Pages
12925-12930
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2083047610
Cited by
290
References
50
Citations by year
2026: 14 · 2025: 21 · 2024: 15 · 2023: 20 · 2022: 17 · 2021: 23 · 2020: 22 · 2019: 26 · 2018: 15 · 2017: 14 · 2016: 26 · 2015: 22 · 2014: 19 · 2013: 18 · 2012: 16
FWCI
5.66
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS057536)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
GPR56, type III collagen, COL3A1, G protein-coupled receptor ligands, cortical lamination, cortical development, neuronal migration, cobblestone lissencephaly, adhesion GPCRs, RhoA signaling, cerebral cortex malformation
MeSH terms
Animals, Basement Membrane, Brain, Cell Movement, Cells, Cultured, Cerebral Cortex, Humans, Immunohistochemistry, Neurons, Protein Binding, Recombinant Proteins, Immunoblotting, Microscopy, Immunoelectron, Mice, Knockout, rhoA GTP-Binding Protein, Collagen Type III, NIH 3T3 Cells, Receptors, G-Protein-Coupled, GTP-Binding Protein alpha Subunits, G12-G13, Immunoprecipitation, Mice, Cobblestone Lissencephaly

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