Active surface transport of metabotropic glutamate receptors through binding to microtubules and actin flow.
Receptors for neurotransmitters are concentrated and stabilized at given sites such as synapses through interactions with scaffolding proteins and cytoskeletal elements. The transport of receptors first involves directed vesicular trafficking of intracellularly stored receptors followed by their targeting to the plasma membrane. Once expressed at the cell surface, receptors are thought to reach their final location by random Brownian diffusion in the plasma membrane plane. Here, we investigate whether the metabotropic glutamate receptor mGluR5 can also be transported actively on the cell surface. We used single particle tracking to follow mGluR5 movement in real time at the surface of neuronal growth cones or fibroblast lamellipodia, both of which bear a particularly active cytoskeleton. We found that after a certain lag time mGluR5 undergoes directed rearward transport, which depends on actin flow. On actin depolymerization, directed movement was suppressed, but receptors still bound to a rigid structure. By contrast, receptor transport and immobilization was fully suppressed by microtubule depolymerization but favored by microtubule stabilization. Furthermore, mGluR5 could be immunoprecipitated with tubulin from rat brains, confirming the ability of mGluR5 to bind to microtubules. We propose that mGluR5 can be transported on the cell surface through actin-mediated retrograde transport of microtubules. This process may play a role in receptor targeting and organization during synapse formation or during glutamate-mediated growth cone chemotaxis.
Serge
Arnauld
A
Physiologie Cellulaire de la Synapse, CNRS UMR 5091, Institut François Magendie, rue Camille saint Saëns, 33077 Bordeaux, Cedex, France.
Fourgeaud
Lawrence
L
Hemar
Agnes
A
Choquet
Daniel
D
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism*; D004622:Embryo, Mammalian; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D018715:Microscopy, Video; D008870:Microtubules / Q000378:metabolism; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014404:Tubulin