High affinity binding of Dab1 to Reelin receptors promotes normal positioning of upper layer cortical plate neurons

Brain Research. Molecular Brain Research
T M Herrick, Jonathan A Cooper

Abstract

The positions of neurons in the neocortex, hippocampus, cerebellum and various other laminated brain regions are regulated by a signaling pathway initiated by the secreted protein Reelin and requiring the intracellular adaptor protein Dab1. Dab1 and the Reelin receptors VLDLR and ApoER2 are expressed by neurons whose migrations are coordinated by Reelin. In vitro, Dab1 binds with high affinity to the cytoplasmic tails of VLDLR and ApoER2 via its PTB domain. To test the importance of Dab1 binding to VLDLR and ApoER2, we replaced the Dab1 gene with a cDNA cassette encoding a point mutant allele, Dab1(F158V). This mutation strongly decreases Dab1 binding in vitro to peptides containing the ApoER2 or VLDLR cytoplasmic regions. Surprisingly, Dab1(F158V/F158V) homozygotes have no discernable phenotype. However, Dab1(F158V/-) hemizygous animals have a subtle phenotype in which late-generated cortical plate neurons migrate excessively into the marginal zone. Early cortical plate neurons, subplate neurons, hippocampal pyramidal cells and cerebellar Purkinje cells are positioned normally. Thus Dab(F158V) is a weak loss-of-function (hypomorphic) allele that has no detectable effect when homozygous. The phenotype of Dab1(F158V/-) hemizygot...Continue Reading

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Citations

Apr 18, 2008·The Cerebellum·Grant W Anderson
Nov 5, 2008·Molecular and Cellular Biology·Libing Feng, Jonathan A Cooper
Sep 20, 2006·Molecular and Cellular Biology·Matthew J SmithTony Pawson
Apr 8, 2014·PloS One·Pablo SoteloMaría-Paz Marzolo
Sep 13, 2008·Molecular and Cellular Neurosciences·Carmen Díaz-RuizEduardo Soriano
Dec 17, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jean-Philippe Rey, Debra L Ellies
Sep 11, 2007·Brain Research·Sarah A MacLaurinKenneth N Fish
May 11, 2005·Biochemical and Biophysical Research Communications·Yongcheng HuangLakhu Keshvara
Jun 12, 2013·Cerebral Cortex·Joanne M BrittoSeong-Seng Tan
Jul 12, 2018·IEEE Transactions on Medical Imaging·Alexej GossmannYu-Ping Wang
Sep 5, 2006·The Journal of Biological Chemistry·Hyang-Sook HoeG William Rebeck

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