Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage.
Reelin-Disabled-1 (Dab1) signaling has a well-established role in regulating neuronal migration during brain development. Binding of Reelin to its receptors induces Dab1 tyrosine phosphorylation. Tyrosine-phosphorylated Dab1 recruits a wide range of SH2 domain-containing proteins and activates multiple signaling cascades, resulting in cytoskeleton remodeling and precise neuronal positioning. In this review, we summarize recent progress in the Reelin-Dab1 signaling field. We focus on Dab1 alternative splicing as a mechanism for modulating the Reelin signal in developing brain. We suggest that correct positioning of neurons in the developing brain is at least partly controlled by alternatively-spliced Dab1 isoforms that differ in the number and type of tyrosine phosphorylation motifs that they contain. We propose a model whereby different subsets of SH2 domain-containing proteins are activated by different Dab1 isoforms, resulting in coordinated migration of neurons.
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada. zgao@ualberta.ca
Zhihua
Z
Gao
Roseline
R
Godbout
D017398:Alternative Splicing; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement; D016764:Cell Polarity; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000737:chemistry*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D014443:Tyrosine; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D046988:Proteasome Endopeptidase Complex