Marlin-1 and conventional kinesin link GABAB receptors to the cytoskeleton and regulate receptor transport

Mol Cell Neurosci. 2007 Jul;35(3):501-12. doi: 10.1016/j.mcn.2007.04.008. Epub 2007 May 1.

Abstract

The cytoskeleton and cytoskeletal motors play a fundamental role in neurotransmitter receptor trafficking, but proteins that link GABA(B) receptors (GABA(B)Rs) to the cytoskeleton have not been described. We recently identified Marlin-1, a protein that interacts with GABA(B)R1. Here, we explore the association of GABA(B)Rs and Marlin-1 to the cytoskeleton using a combination of biochemistry, microscopy and live cell imaging. Our results indicate that Marlin-1 is associated to microtubules and the molecular motor kinesin-I. We demonstrate that a fraction of Marlin-1 is mobile in dendrites of cultured hippocampal neurons and that mobility is microtubule-dependent. We also show that GABA(B)Rs interact robustly with kinesin-I and that intracellular membranes containing GABA(B)Rs are sensitive to treatments that disrupt a protein complex containing Marlin-1, kinesin-I and tubulin. Finally, we report that a kinesin-I mutant severely impairs receptor transport. We conclude that Marlin-1 and kinesin-1 link GABA(B)Rs to the tubulin cytoskeleton in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cells, Cultured
  • Cytoskeleton / physiology*
  • Embryo, Mammalian
  • Female
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Kinesins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neurons / drug effects
  • Neurons / metabolism
  • Nocodazole / pharmacology
  • Pregnancy
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA / metabolism*
  • Time Factors
  • Transfection

Substances

  • Antineoplastic Agents
  • Jakmip1 protein, rat
  • RNA-Binding Proteins
  • Receptors, GABA
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Kinesins
  • Nocodazole