Abstract
AMPA receptor (AMPAR) function is modulated by auxiliary subunits. Here, we report on three AMPAR interacting proteins-namely CKAMP39, CKAMP52 and CKAMP59-that, together with the previously characterized CKAMP44, constitute a novel family of auxiliary subunits distinct from other families of AMPAR interacting proteins. The new members of the CKAMP family display distinct regional and developmental expression profiles in the mouse brain. Notably, despite their structural similarities they exert diverse modulation on AMPAR gating by influencing deactivation, desensitization and recovery from desensitization, as well as glutamate and cyclothiazide potency to AMPARs. This study indicates that AMPAR function is very precisely controlled by the cell-type specific expression of the CKAMP family members.
Highlights
AMPARs mediate the majority of fast excitatory transmission in the central nervous system and play a key role in brain plasticity
Several labs have employed large proteomic screens to search for AMPAR interacting proteins, which resulted in the identification of new AMPAR auxiliary subunits, such as CKAMP44, cornichons (Schwenk et al, 2009) and GSG1L (Schwenk et al, 2012; Shanks et al, 2012)
All CKAMPs exhibited a significant homology in the region of CKAMP44 that is necessary for AMPAR binding (Khodosevich et al, 2014)
Summary
AMPARs mediate the majority of fast excitatory transmission in the central nervous system and play a key role in brain plasticity. AMPAR function is controlled by a multitude of auxiliary subunits (Yan and Tomita, 2012) These include TARPs (Tomita et al, 2003), cornichons (Schwenk et al, 2009), Sol-1 (Zheng et al, 2004) and SynDIG1 (Kalashnikova et al, 2010). Since auxiliary subunits are differentially expressed in the brain, the specific combination in a particular cell type is likely to govern the AMPAR response to glutamate, as is the case for dentate gyrus granule cells, which express TARP g-8 and CKAMP44. Both proteins increase the number of AMPARs on the cell surface, decrease the deactivation rate and increase glutamate affinity. They differ in the influence that they extend on AMPAR desensitization, recovery from desensitization, longterm and short-term potentiation (Khodosevich et al, 2014)
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