Synaptic localization of neuroligin 2 in the rodent retina: Comparative study with the dystroglycan‐containing complex

Abstract

Several recent studies have shown that neuroligin 2 (NL2), a component of the cell adhesion neurexins-neuroligins complex, is localized postsynaptically at hippocampal and other inhibitory synapses throughout the brain. Other studies have shown that components of the dystroglycan complex are also localized at a subset of inhibitory synapses and are coexpressed with NL2 in brain. These data prompted us to undertake a comparative study between the localization of NL2 and the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA is expressed both in the inner and in the outer nuclear layers. Second, we found that NL2 is localized both in the inner and in the outer synaptic plexiform layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive colocalization with RIM2, a component of the presynaptic active zone at ribbon synapses, argue that NL2 is localized presynaptically at photoreceptor terminals. Third, comparison of NL2 and the dystroglycan complex distribution patterns reveals that, despite their coexpression in the outer plexiform layer, they are spatially segregated within distinct domains of the photoreceptor terminals, where NL2 is selectively associated with the active zone and the dystroglycan complex is distally distributed in the lateral regions. Finally, we report that the dystroglycan deficiency in the mdx(3cv) mouse does not alter NL2 localization in the outer plexiform layer. These data show that the NL2- and dystroglycan-containing complexes are differentially localized in the presynaptic photoreceptor terminals and suggest that they may serve distinct functions in retina.

Alternative splicing of neuroligin and its protein distribution in the outer plexiform layer of the chicken retina

“…Mouse anti‐islet1 recognizes both Islet‐1 and ‐2 and has a well‐established pattern of cell labeling by IHC and in situ hybridization (ISH) in chicken motor and retinal neurons (Tsuchida et al,1994; Fischer and Reh,2002). The specificity of anti‐Lim1/2 antibodies was verified by IHC and ISH showing specific expression in only a subset of horizontal cells as previously reported (Tsuchida et al,1994; Lui et al,2010). Lim3 antibodies label bipolar cells by IHC equivalent to patterns observed by ISH (Tsuchida et al,1994; Zhadanov et al,1995; Ericson et al,1997; Glasgow et al,1997; Edqvist and Hallbook,2004; Edqvist et al,2006).…”

“…The specificity of anti‐Lim1/2 antibodies was verified by IHC and ISH showing specific expression in only a subset of horizontal cells as previously reported (Tsuchida et al,1994; Lui et al,2010).…”

“…Alternatively, there are an increasing number of examples where posttranscriptional regulation of protein synthesis limits the translation of mRNA (Decembrini et al,2006; Filipowicz et al,2008). As for NLGN2, it is expressed in both the outer and inner nuclear layers of the mouse retina, where, in addition to being present at inhibitory sites alongside components of the dystroglycan complex in the inner plexiform layer, it is found at presynaptic terminals of photoreceptor ribbon synapses (Lui et al,2010). Since inhibitory GABA receptors are also expressed by photoreceptors, this finding is not altogether surprising except for the fact that thus far we have been unable to identify NLGN2 in the chicken, let alone their photoreceptors.…”

Dystroglycan Binding to α-Neurexin Competes with Neurexophilin-1 and Neuroligin in the Brain

“…Unlike Nrxn variants that are expressed in most excitatory and inhibitory neurons ( 43 ), the α-Nrxn-specific ligand Nxph1 is restricted to inhibitory interneurons ( 36 , 44 ), similar to αDAG, which also prefers subsets of inhibitory synapses where it may co-localize with Nlgn2 ( 45 – 48 ). Nxphs comprise a family of glycoproteins (Nxph1–4) that exhibit characteristics of secreted, preproprotein-derived molecules ( 35 , 36 ), but the structural determinants of their interaction with LNS2 ( 34 ) are still unclear.…”

Electroretinography and exploration of visual and auditory function in mutant mice with synaptic defects

“…Hoon et al concluded, that NL2 deficiency in the end causes a decrease of functionally intact GABA A receptors. Lui et al in 2010 showed that NL2 was also localized presynapically within the ribbon synapseactive zone complex of the photoreceptor terminals. In their results, NL2 was not associated with inhibitory GABAergic synapses in the OPL.…”