Marlin-1 and conventional kinesin link GABAB receptors to the cytoskeleton and regulate receptor transport.
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.
Mesh Terms:
Animals, Antineoplastic Agents, Cells, Cultured, Cytoskeleton, Embryo, Mammalian, Female, Green Fluorescent Proteins, Hippocampus, Kinesin, Mice, Mice, Inbred BALB C, Neurons, Nocodazole, Pregnancy, Protein Transport, RNA-Binding Proteins, Rats, Rats, Sprague-Dawley, Receptors, GABA, Time Factors, Transfection
Animals, Antineoplastic Agents, Cells, Cultured, Cytoskeleton, Embryo, Mammalian, Female, Green Fluorescent Proteins, Hippocampus, Kinesin, Mice, Mice, Inbred BALB C, Neurons, Nocodazole, Pregnancy, Protein Transport, RNA-Binding Proteins, Rats, Rats, Sprague-Dawley, Receptors, GABA, Time Factors, Transfection
Mol. Cell. Neurosci.
Date: Jul. 01, 2007
PubMed ID: 17532644
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