Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites.
In cells, molecular motors operate in polarized sorting of molecules, although the steering mechanisms of motors remain elusive. In neurons, the kinesin motor conducts vesicular transport such as the transport of synaptic vesicle components to axons and of neurotransmitter receptors to dendrites, indicating that vesicles may have to drive the motor for the direction to be correct. Here we show that an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor subunit--GluR2-interacting protein (GRIP1)--can directly interact and steer kinesin heavy chains to dendrites as a motor for AMPA receptors. As would be expected if this complex is functional, both gene targeting and dominant negative experiments of heavy chains of mouse kinesin showed abnormal localization of GRIP1. Moreover, expression of the kinesin-binding domain of GRIP1 resulted in accumulation of the endogenous kinesin predominantly in the somatodendritic area. This pattern was different from that generated by the overexpression of the kinesin-binding scaffold protein JSAP1 (JNK/SAPK-associated protein-1, also known as Mapk8ip3), which occurred predominantly in the somatoaxon area. These results indicate that directly binding proteins can determine the traffic direction of a motor protein.
Setou
Mitsutoshi
M
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Seog
Dae-Hyung
DH
Tanaka
Yosuke
Y
Kanai
Yoshimitsu
Y
Takei
Yosuke
Y
Kawagishi
Masahiko
M
Hirokawa
Nobutaka
N
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016547:Kinesins; C104722:glutamate receptor ionotropic, AMPA 2