Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking.
Although membrane trafficking pathways are involved in basic cellular functions, the evolutionally expanded number of their related family proteins suggests additional roles for membrane trafficking in higher organisms. Here, we show that several Rab-dependent trafficking pathways differentially participate in neuronal migration, an essential step for the formation of the mammalian-specific six-layered brain structure. In vivo electroporation-mediated suppression of Rab5 or dynamin to block endocytosis caused a severe neuronal migration defect in mouse cerebral cortex. Among many downstream endocytic pathways, suppression of Rab11-dependent recycling pathways exhibited a similar migration disorder, whereas inhibition of Rab7-dependent lysosomal degradation pathways affected only the final phase of neuronal migration and dendrite morphology. Inhibition of Rab5 or Rab11 perturbed the trafficking of N-cadherin, whose suppression also disturbed neuronal migration. Taken together, our findings reveal physiological roles of endocytic pathways, each of which has specific functions in distinct steps of neuronal migration and maturation during mammalian brain formation.
Kawauchi
Takeshi
T
Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan. takeshi-kawauchi@umin.ac.jp
Sekine
Katsutoshi
K
Shikanai
Mima
M
Chihama
Kaori
K
Tomita
Kenji
K
Kubo
Ken-ichiro
K
Nakajima
Kazunori
K
Nabeshima
Yo-Ichi
Y
Hoshino
Mikio
M
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
D015820:Cadherins; D034281:Dynamins; D048670:MAP Kinase Kinase 4; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C489083:Cdh2 protein, mouse; C000716465:rab7 GTP-binding proteins, mouse