title: SDCCAG8 regulates pericentriolar material recruitment and neuronal migration in the developing cortex.
abstract: Mutations of SDCCAG8 are associated with nephronophthisis and Bardet-Biedl syndrome, as well as schizophrenia; however, the function of SDCCAG8 remains largely unknown. Here, we show that SDCCAG8 regulates centrosomal accumulation of pericentriolar material and neuronal polarization and migration in the developing mouse cortex. Sdccag8 expression is selectively elevated in newborn neurons prior to their commencement of radial locomotion, and suppression of this expression by short-hairpin RNAs or a loss-of-function allele impairs centrosomal recruitment of γ-tubulin and pericentrin, interferes with microtubule organization, decouples the centrosome and the nucleus, and disrupts neuronal migration. Moreover, SDCCAG8 interacts and cotraffics with pericentriolar material 1 (PCM1), a centriolar satellite protein crucial for targeting proteins to the centrosome. Expression of SDCCAG8 carrying a human mutation causes neuronal migration defects. These results reveal a critical role for SDCCAG8 in controlling centrosomal properties and function, and provide insights into the basis of neurological defects linked to SDCCAG8 mutations.
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Neuroscience Graduate Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Insolera
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; BCMB Graduate Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Division of Nephrology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Rannar
authors.initials: R
authors.lastname: Airik
authors.affiliation: Division of Nephrology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Neuroscience Graduate Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; BCMB Graduate Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shis@mskcc.org.
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018385:Centrosome / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development*; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D000941:Antigens; D001324:Autoantigens; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; C490114:Pcm1 protein, mouse; D034741:RNA, Small Interfering; C472381:Sdccag8 protein, mouse; D014404:Tubulin; C086178:pericentrin
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