Coxsackievirus and adenovirus receptor (CAR) mediates trafficking of acid sensing ion channel 3 (ASIC3) via PSD-95.
We have previously shown that the Coxsackievirus and adenovirus receptor (CAR) can interact with post-synaptic density 95 (PSD-95) and localize PSD-95 to cell-cell junctions. We have also shown that activity of the acid sensing ion channel (ASIC3), a H(+)-gated cation channel that plays a role in mechanosensation and pain signaling, is negatively modulated by PSD-95 through a PDZ-based interaction. We asked whether CAR and ASIC3 simultaneously interact with PSD-95, and if so, whether co-expression of these proteins alters their cellular distribution and localization. Results indicate that CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. CAR also brings both PSD-95 and ASIC3 to the junctions of heterologous cells. Moreover, CAR rescues PSD-95-mediated inhibition of ASIC3 currents. These data suggest that, in addition to activity as a viral receptor and adhesion molecule, CAR can play a role in trafficking proteins, including ion channels, in a PDZ-based scaffolding complex.
Department of Biological Sciences, Wright State University, Dayton, OH 45435, USA. katherine.excoffon@wright.edu
Katherine J D A
KJ
Excoffon
Abimbola O
AO
Kolawole
Nobuyoshi
N
Kusama
Nicholas D
ND
Gansemer
Priyanka
P
Sharma
Alesia M
AM
Hruska-Hageman
Elena
E
Petroff
Christopher J
CJ
Benson
D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains; D021381:Protein Transport
C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins