Reelin binds alpha3beta1 integrin and inhibits neuronal migration.
Mice that are mutant for Reelin or Dab1, or doubly mutant for the VLDL receptor (VLDLR) and ApoE receptor 2 (ApoER2), show disorders of cerebral cortical lamination. How Reelin and its receptors regulate laminar organization of cerebral cortex is unknown. We show that Reelin inhibits migration of cortical neurons and enables detachment of neurons from radial glia. Recombinant and native Reelin associate with alpha3beta1 integrin, which regulates neuron-glia interactions and is required to achieve proper laminar organization. The effect of Reelin on cortical neuronal migration in vitro and in vivo depends on interactions between Reelin and alpha3beta1 integrin. Absence of alpha3beta1 leads to a reduction of Dab1, a signaling protein acting downstream of Reelin. Thus, Reelin may arrest neuronal migration and promote normal cortical lamination by binding alpha3beta1 integrin and modulating integrin-mediated cellular adhesion.
Dulabon
L
L
Department of Biology and Neuroscience, Pennsylvania State University, University Park 16802, USA.
Olson
E C
EC
Taglienti
M G
MG
Eisenhuth
S
S
McGrath
B
B
Walsh
C A
CA
Kreidberg
J A
JA
Anton
E S
ES
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism* / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D039201:Integrin alpha3beta1; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology*; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D039201:Integrin alpha3beta1; D016023:Integrins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases