NDLI: Proper Level of Cytosolic Disabled-1, Which Is Regulated by Dual Nuclear Translocation Pathways, Is Important for Cortical Neuronal Migration.

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Proper Level of Cytosolic Disabled-1, Which Is Regulated by Dual Nuclear Translocation Pathways, Is Important for Cortical Neuronal Migration.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Honda, Takao Nakajima, Kazunori
Description	Country affiliation: Japan Author Affiliation: Honda T ( Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.); Nakajima K ( Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.)
Abstract	Disabled-1 (Dab1) is an essential intracellular protein in the Reelin pathway. It has a nuclear localization signal (NLS; hereafter referred to as 'NLS1') and 2 nuclear export signals, and shuttles between the nucleus and the cytoplasm. In this study, we found that Dab1 has an additional unidentified NLS, and that the Dab1 NLS1 mutant could translocate to the nucleus in an unconventional ATP/temperature-dependent and cytoplasmic factor/RanGTP gradient-independent manner. Additional mutations in the NLS1 mutant revealed that K(67) and K(69) are important for the nuclear transport. Furthermore, an excess of the intracellular domain of the Reelin receptors inhibited the nuclear translocation of Dab1. An in utero electroporation study showed that a large amount of Dab1 in the cytoplasm in migrating neurons inhibited the migration, and that forced transport of Dab1 into the nucleus attenuated this inhibitory effect. In addition, rescue experiments using yotari, an autosomal recessive mutant of dab1, revealed that cells expressing Dab1 NLS1 mutant tend to distribute at more superficial positions than those expressing wild-type Dab1. Taken together, these findings suggest that Dab1 has at least 2 NLSs, and that the regulation of the subcellular localization of Dab1 is important for the proper migration of excitatory neurons.
File Format	HTM / HTML
ISSN	10473211
e-ISSN	14602199
Journal	Cerebral Cortex
Issue Number	7
Volume Number	26
Language	English
Publisher	Oxford University Press
Publisher Date	2016-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Neuroscience Discipline Neurology
Content Type	Text
Resource Type	Article
Subject	Cognitive Neuroscience Cellular and Molecular Neuroscience

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