title: RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex.
abstract: BACKGROUND
  Loss of function mutations in RAB18, has been identified in patients with the human neurological and developmental disorder Warburg Micro syndrome. However, the function of RAB18 in brain remains unknown.
  
  
  RESULTS
  In this study, we report that RAB18 is a critical regulator of neuronal migration and morphogenesis. Using in utero electroporation suppression of RAB18 in the mouse brain impairs radial migration. Overexpression of dominant negative RAB18 or disruption of RAB3GAP (RAB18GEF) also results in delayed neuronal migration in the developing mouse cortex and inhibition of neurite growth in vitro. Moreover, loss of RAB18 induces an acceleration of N-cadherin degradation by lysosomal pathway resulting in the decrease of surface level of N-cadherin on neurons.
  
  
  CONCLUSIONS
  RAB18 regulates neuronal migration and morphogenesis during development. Our findings highlight the critical role of RAB3GAP-RAB18 pathway in the developing cerebral cortex and might explain some of clinical features observed in patients with Warburg Micro syndrome.
authors.affiliation: Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. qwwu398@hotmail.com.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. qwwu398@hotmail.com.|Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. qwwu398@hotmail.com.
authors.forename: Qinwei
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. xiaqinsun@bjmu.edu.cn.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. xiaqinsun@bjmu.edu.cn.
authors.forename: Xiaqin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. dryue@bjmu.edu.cn.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. dryue@bjmu.edu.cn.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. tianlan_lu@126.com.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. tianlan_lu@126.com.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. ruanyanyan@126.com.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. ruanyanyan@126.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. tiandachen@bjmu.edu.cn.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. tiandachen@bjmu.edu.cn.
authors.forename: Tianda
authors.initials: T
authors.lastname: Chen
authors.affiliation: Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. daizhang@bjmu.edu.cn.|Peking University Sixth Hospital/Institute of Mental Health, Beijing, 100191, China. daizhang@bjmu.edu.cn.|National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. daizhang@bjmu.edu.cn.|PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. daizhang@bjmu.edu.cn.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000015:Abnormalities, Multiple / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002386:Cataract / Q000151:congenital* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology / Q000473:pathology*; D003315:Cornea / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007006:Hypogonadism / Q000378:metabolism* / Q000473:pathology*; D008607:Intellectual Disability / Q000378:metabolism* / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism; D008831:Microcephaly / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009896:Optic Atrophy / Q000378:metabolism* / Q000473:pathology*; D059748:Proteolysis; D020691:rab GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; C083879:Rab18 protein, mouse; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins