Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation.
The regulated trafficking of neurotransmitter receptors at synapses is critical for synaptic function and plasticity. However, the molecular machinery that controls active transport of receptors into synapses is largely unknown. We found that, in rat hippocampus, the insertion of AMPA receptors (AMPARs) into spines during synaptic plasticity requires a specific motor protein, which we identified as myosin Va. We found that myosin Va associates with AMPARs through its cargo binding domain. This interaction was enhanced by active, GTP-bound Rab11, which is also transported by the motor protein. Myosin Va mediated the CaMKII-triggered translocation of GluR1 receptors from the dendritic shaft into spines, but it was not required for constitutive GluR2 trafficking. Accordingly, myosin Va was specifically required for long-term potentiation, but not for basal synaptic transmission. In summary, we identified the specific motor protein and organelle acceptor that catalyze the directional transport of AMPARs into spines during activity-dependent synaptic plasticity.
Correia
Susana S
SS
Department of Pharmacology, University of Michigan Medical School, 1150 W. Medical Center Dr., Ann Arbor, Michigan 48109-0632, USA.
Bassani
Silvia
S
Brown
Tyler C
TC
Lisé
Marie-France
MF
Backos
Donald S
DS
El-Husseini
Alaa
A
Passafaro
Maria
M
Esteban
José A
JA
D000818:Animals; D002478:Cells, Cultured; D050660:Core Binding Factors / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D050660:Core Binding Factors; D020409:Molecular Motor Proteins; C513081:Myo5a protein, rat; D018091:Receptors, AMPA; C492252:Wdr44 protein, rat; D019204:GTP-Binding Proteins; D024701:Myosin Type V; D018995:Myosin Heavy Chains