SARA regulates neuronal migration during neocortical development through L1 trafficking. Academic Article uri icon

Overview

abstract

  • Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppression-induced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.

publication date

  • July 28, 2016

Research

keywords

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neocortex
  • Neural Cell Adhesion Molecule L1
  • Neurons
  • Serine Endopeptidases

Identity

PubMed Central ID

  • PMC5047672

Scopus Document Identifier

  • 84984843715

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2007.05.030

PubMed ID

  • 27471254

Additional Document Info

volume

  • 143

issue

  • 17