SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 glutamate receptors in Caenorhabditis elegans

Abstract

Most rapid excitatory synaptic signaling in the brain is mediated by postsynaptic ionotropic glutamate receptors (iGluRs) that are gated open by the neurotransmitter glutamate. In Caenorhabditis elegans, sol-1 encodes a CUB-domain transmembrane protein that is required for currents that are mediated by the GLR-1 iGluR. Mutations in sol-1 do not affect GLR-1 expression, localization, membrane insertion, or stabilization at synapses, suggesting that SOL-1 is required for iGluR function. Here, we provide evidence that SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 receptors. We show that mutant variants of GLR-1 with altered gating partially restore glutamate-gated current and GLR-1-dependent behaviors in sol-1 mutants. Domain analysis of SOL-1 indicates that extracellular CUB domain 3 is required for function and that a secreted variant partially restores glutamate-gated currents and behavior. Also, we show that endogenous glutamatergic synaptic currents are absent in sol-1 mutants. Our data suggest that GLR-1 iGluRs are not simply stand-alone molecules and require the SOL-1 auxiliary protein to promote the open state of the receptor. Our analysis presents the possibility that glutamatergic signaling in other organisms may be similarly modified by SOL-1-like transmembrane proteins. Most fast synaptic neurotransmission in the vertebrate central nervous system is mediated by ionotropic glutamate receptors (iGluRs) that are gated by the neurotransmitter glutamate. The non-NMDA class of iGluRs are gated by the ligand ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainate (1). Recently, SOL-1 was shown to be specifically required for non-NMDA-type glutamate-gated currents mediated by the Caenorhabditis elegans iGluR GLR-1 (2). Transgenic worms that express the gain-of-function GLR-1(A687T) (referred to as the lurcher variant) have forward movements that are much briefer than WT, causing a ''lurching'' phenotype (2, 3). In sol-1 mutants, the lurching behavior is suppressed, and kainate-gated currents are absent. In contrast, NMDA-dependent currents (4), are not disrupted in sol-1 mutants. How SOL-1 contributes to glutamate-gated currents is not well understood. SOL-1 and GLR-1 colocalize at puncta in ventral cord processes that are presumed to be points of synaptic contact. Furthermore, coimmunoprecipitation experiments indicate that SOL-1 and GLR-1 form a complex in COS-7 cells (2). These data suggest that SOL-1 may function as a GLR-1 auxiliary subunit.In sol-1 mutants, GLR-1 is expressed on the cell surface, but the mutants have a phenotype that is consistent with disrupted glutamatergic neurotransmission. Furthermore, no kainate-gated currents can be recorded from the AVA interneurons, suggesting that SOL-1 could modify ligand-binding or receptor gating, which is defined broadly here to include the transitions between closed, open, and desensitized states. We have addressed these possibilities by using two genetic strategies. First, we generated a series of truncated versions of SOL...

Synaptic AMPA receptor composition in development, plasticity and disease

“…Currently identified AMPAR auxiliary subunits include TARPs, suppressor of lurcher (SOL) 110 , Cornichon homologues (CNIHs) 111 , synapse differentiation-induced genes (SynDIG I and SynDIG4) 112,113 , cysteine-knot AMPAR modulating protein family 114,115 , and germ cell-specific gene 1-like (GSG1L) protein 116 . Of these the prototypical TARP family of AMPAR auxiliary subunits are by far the best characterized.…”

Neuronal Activity and CaMKII Regulate Kinesin-Mediated Transport of Synaptic AMPARs

“…In mutants where a component of the complex has been disrupted, such as the GLR-1 subunit, the ratio of forward to backward movement is altered, thus disrupting foraging behavior (de Bono and Maricq, 2005; Zheng et al, 1999) as well as the avoidance response to tactile and osmotic stimuli (Hart et al, 1995; Maricq et al, 1995). We identified many of the molecular components of the GLR-1 signaling complex, including the GLR-2 AMPAR subunit, and the auxiliary proteins SOL-1, SOL-2 and STG-2, and determined how they contribute to postsynaptic function and the control of behavior (Brockie et al, 2013; Brockie et al, 2001; Mellem et al, 2002; Walker et al, 2006b; Wang et al, 2012; Wang et al, 2008; Zheng et al, 2006; Zheng et al, 2004). …”

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

“…However, an important difference between TARPs and STG-1 and STG-2 is the obligatory requirement of an additional transmembrane auxiliary subunit (SOL-1) that is structurally unrelated to TARPs and interacts directly with invertebrate AMPA receptor subunits (GLR-1 and GLR-2) to slow and reduce the extent of receptor desensitization (Zheng et al, 2006;Walker et al, 2006a,b).…”