Involvement of myosin Vb in glutamate receptor trafficking.
Myosin V motors mediate cargo transport; however, the identity of neuronal molecules transported by these proteins remains unknown. Here we show that myosin Vb is expressed in several neuronal populations and associates with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor subunit GluR1. In developing hippocampal neurons, expression of the tail domain of myosin Vb, but not myosin Va, enhanced GluR1 accumulation in the soma and reduced its surface expression. These changes were accompanied by reduced GluR1 clustering and diminished frequency of excitatory but not inhibitory synaptic currents. Similar effects were observed upon expression of full-length myosin Vb lacking a C-terminal region required for binding to the small GTPase Rab11. In contrast, mutant myosin Vb did not change the localization of several other neurotransmitter receptors, including the glutamate receptor subunit NR1. These results reveal a novel mechanism for the transport of a specific glutamate receptor subunit in neurons mediated by a member of the myosin V family.
Lisé
Marie-France
MF
Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Wong
Tak Pan
TP
Trinh
Alex
A
Hines
Rochelle M
RM
Liu
Lidong
L
Kang
Rujun
R
Hines
Dustin J
DJ
Lu
Jie
J
Goldenring
James R
JR
Wang
Yu Tian
YT
El-Husseini
Alaa
A
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D009154:Mutation; D024701:Myosin Type V / Q000737:chemistry; D009218:Myosins / Q000737:chemistry*; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism; D013347:Subcellular Fractions; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D018076:DNA, Complementary; D005982:Glutathione Transferase; D024701:Myosin Type V; D009218:Myosins; D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C101826:Myo5b protein, rat