Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking

Neuron. 2010 Aug 26;67(4):588-602. doi: 10.1016/j.neuron.2010.07.007.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion / physiology
  • Cell Communication / physiology
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / physiology
  • Dendrites / physiology
  • Dynamins / genetics
  • Dynamins / metabolism
  • Endocytosis / physiology*
  • Lysosomes / enzymology
  • Lysosomes / physiology
  • MAP Kinase Kinase 4 / metabolism
  • Mice
  • Mice, Inbred ICR
  • Neurons / cytology
  • Neurons / physiology*
  • Signal Transduction
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism

Substances

  • Cadherins
  • Cdh2 protein, mouse
  • rab7 protein
  • MAP Kinase Kinase 4
  • rab11 protein
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins
  • Dynamins