Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system

Mol Cell Neurosci. 2001 Sep;18(3):307-19. doi: 10.1006/mcne.2001.1022.

Abstract

Doublecortin is a microtubule-associated protein required for normal corticogenesis in the developing brain. We carried out a yeast two-hybrid screen to identify interacting proteins. One of the isolated clones encodes the mu1 subunit of the adaptor complex AP-1 involved in clathrin-dependent protein sorting. We found that Doublecortin also interacts in yeast with mu2 from the AP-2 complex. Mutagenesis and pull-down experiments showed that these interactions were mediated through a tyrosine-based sorting signal (YLPL) in the C-terminal part of Doublecortin. The functional relevance of these interactions was suggested by the coimmunoprecipitation of Doublecortin with AP-1 and AP-2 from mouse brain extracts. This interaction was further supported by RNA in situ hybridization and immunofluorescence studies. Taken together these data indicate that a certain proportion of Doublecortin interacts with AP-1 and/or AP-2 in vivo and are consistent with a potential involvement of Doublecortin in protein sorting or vesicular trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 1*
  • Adaptor Protein Complex 2*
  • Adaptor Protein Complex 3*
  • Adaptor Protein Complex mu Subunits*
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Cells, Cultured
  • Clathrin / metabolism*
  • Clathrin / physiology
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / physiology
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Microtubule-Associated Proteins*
  • Nervous System / embryology*
  • Nervous System / metabolism*
  • Neuropeptides / metabolism*
  • Neuropeptides / physiology
  • Peptide Fragments / metabolism
  • Peptide Fragments / physiology
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factor AP-1 / metabolism

Substances

  • AP1M1 protein, human
  • AP1M2 protein, human
  • AP3M2 protein, human
  • APM1 protein, S cerevisiae
  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 2
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex mu Subunits
  • Adaptor Proteins, Vesicular Transport
  • Ap1m1 protein, mouse
  • Ap1m2 protein, mouse
  • Ap3m2 protein, mouse
  • Carrier Proteins
  • Clathrin
  • Macromolecular Substances
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor AP-1
  • adaptor protein complex 1, mu 1 subunit
  • adaptor protein complex 1, mu 2 subunit
  • adaptor protein complex 2, mu 1 subunit
  • adaptor protein complex 2, mu 2 subunit
  • doublecortin protein