Here's a SFN paper on "Stargazin" by Drs. Rogers and Varney. Others have published quite a bit on Stargazin over the past several years. Stargazin is a "TARP" or Transmembrane AMPA Receptor Regulatory Protein. These participate in the surface delivery and anchoring of AMPA receptors, and may also act as positive modulators of AMPA receptor ion channel function. It figures that Cortex would get interested in these -
>>> Program#/Poster#: 424.5/C22
Title: Effects of stargazin on allosteric, positive modulators of AMPA receptors (Ampakines)
Location: Georgia World Congress Center: Halls B3-B5
Presentation Start/End Time: Monday, Oct 16, 2006, 1:00 PM - 2:00 PM
Authors: *Y. LI, L. NILSSON, M. A. VARNEY, G. ROGERS;
R & D, Cortex Pharmaceuticals, Inc, Irvine, CA.
Stargazin (STG) was characterized initially by homology as the second member (γ2) of the voltage-gated calcium channel γ subunit family. Recently, it has been reported that STG enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a family of small molecules that increase the currents through AMPA receptors by binding to an allosteric site. The ligands do not have direct agonistic properties, but instead modulate the receptor rate constants for transmitter binding, channel opening, or desensitization. The effects of the Ampakine, CX614 and cyclothiazide (CTZ) were compared on homomeric GluR1-flip receptors expressed on HEK293 cells by transient transfection with or without STG gene. STG dramatically enhanced the surface expression of AMPA receptors. 500 μM Glutamate-induced steady-state currents were increased from 5.4 ± 1.2 pA/pF (n=4) to 125 ± 55 pA/pF (n=4) when STG was co-expressed, and the ratios of 500 μM kainate and 500 μM glutamate activated steady-state currents were increased from 0.58 ± 0.03 to 16.4 ± 6.5. STG speeded the association rates and slowed the dissociation rates for both CX614 and CTZ on desensitized receptors. The estimated Kd value for CX614 was lowered from 340 μM to 70 μM, whereas that for CTZ was lowered from 170 μM to 6 μM by STG. The data suggest that Stargazin can dramatically alter the conformation of the receptor dimer interface where CX614 and CTZ are known to bind.
Disclosures: Y. Li , None; L. Nilsson, None; M.A. Varney, None; G. Rogers, None. <<<
