Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L.
AMPA receptor (AMPA-R) complexes consist of channel-forming subunits, GluA1-4, and auxiliary proteins, including TARPs, CNIHs, synDIG1, and CKAMP44, which can modulate AMPA-R function in specific ways. The combinatorial effects of four GluA subunits binding to various auxiliary subunits amplify the functional diversity of AMPA-Rs. The significance and magnitude of molecular diversity, however, remain elusive. To gain insight into the molecular complexity of AMPA and kainate receptors, we compared the proteins that copurify with each receptor type in the rat brain. This interactome study identified the majority of known interacting proteins and, more importantly, provides candidates for additional studies. We validate the claudin homolog GSG1L as a newly identified binding protein and unique modulator of AMPA-R gating, as determined by detailed molecular, cellular, electrophysiological, and biochemical experiments. GSG1L extends the functional variety of AMPA-R complexes, and further investigation of other candidates may reveal additional complexity of ionotropic glutamate receptor function.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Natalie F
NF
Shanks
Jeffrey N
JN
Savas
Tomohiko
T
Maruo
Ondrej
O
Cais
Atsushi
A
Hirao
Souichi
S
Oe
Anirvan
A
Ghosh
Yasuko
Y
Noda
Ingo H
IH
Greger
John R
JR
Yates
Terunaga
T
Nakagawa
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D057167:Claudins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D008565:Membrane Proteins
D057167:Claudins; D021122:Protein Subunits; D011506:Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C578454:GSG1L protein, rat; D008565:Membrane Proteins