Signal-mediated, AP-1/clathrin-dependent sorting of transmembrane receptors to the somatodendritic domain of hippocampal neurons

Neuron. 2012 Sep 6;75(5):810-23. doi: 10.1016/j.neuron.2012.07.007.

Abstract

Plasma membranes of the somatodendritic and axonal domains of neurons are known to have different protein compositions, but the molecular mechanisms that determine this polarized protein distribution remain poorly understood. Herein we show that somatodendritic sorting of various transmembrane receptors in rat hippocampal neurons is mediated by recognition of signals within the cytosolic domains of the proteins by the μ1A subunit of the adaptor protein-1 (AP-1) complex. This complex, in conjunction with clathrin, functions in the neuronal soma to exclude somatodendritic proteins from axonal transport carriers. Perturbation of this process affects dendritic spine morphology and decreases the number of synapses. These findings highlight the primary recognition event that underlies somatodendritic sorting and contribute to the evolving view of AP-1 as a global regulator of cell polarity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Protein Complex 1 / genetics
  • Adaptor Protein Complex 1 / metabolism*
  • Adaptor Protein Complex mu Subunits / genetics
  • Adaptor Protein Complex mu Subunits / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Polarity / physiology*
  • Clathrin / physiology*
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Humans
  • Molecular Sequence Data
  • Neurons / physiology*
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology*
  • Transgenes / physiology

Substances

  • Adaptor Protein Complex 1
  • Adaptor Protein Complex mu Subunits
  • Ap1m1 protein, mouse
  • Clathrin
  • Receptors, Cell Surface