Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking.
SAP97 is a modular protein composed of three PDZ domains, an SH3 domain, and a guanylate kinase-like domain. It has been implicated functionally in the assembly and structural stability of synaptic junctions as well as in the trafficking, recruitment, and localization of specific ion channels and neurotransmitter receptors. The N terminus of SAP97 (S97N) has been shown to play a key role in the selection of binding partners and the localization of SAP97 at adhesion sites, as well as the clustering of ion channels in heterologous cells. Using the S97N domain as bait in a yeast two-hybrid screen, we identified the minus-end-directed actin-based motor, myosin VI, as an S97N binding partner. Moreover, in light membrane fractions prepared from rat brain, we found that myosin VI and SAP97 form a trimeric complex with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, GluR1. These data suggest that SAP97 may serve as a molecular link between GluR1 and the actin-dependent motor protein myosin VI during the dynamic translocation of AMPA receptors to and from the postsynaptic plasma membrane.
Wu
Hongju
H
Department of Neurobiology, University of Alabama, Birmingham, AL 35294-0021, USA.
Nash
Joanne E
JE
Zamorano
Pedro
P
Garner
Craig C
CC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D018938:Caco-2 Cells; D000074288:Discs Large Homolog 1 Protein; D006801:Humans; D008565:Membrane Proteins; D025121:Myosin Type IV / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D025121:Myosin Type IV; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C513314:DLG1 protein, human; C501119:Dlg1 protein, rat