Differential distribution and developmental expression of synaptic vesicle protein 2 isoforms in the mouse retina

Abstract

Synaptic vesicle protein 2 (SV2), a ubiquitous synaptic vesicle protein, is known to participate in the regulation of Ca(2+)-mediated synaptic transmission, although its precise function has not been established. Three SV2 isoforms (SV2A, SV2B, SV2C) have been identified recently, each of which has a unique distribution in brain, suggesting synapse-specific functions. To determine if SV2A, -B, and -C are differentially distributed among synapses in the retina and the sequence of their development, we examined their distribution and expression patterns immunocytochemically in adult and developing mouse retina. The three SV2 isoforms were differentially distributed in the synapses of the two plexiform layers in the adult retina. SV2A was present in cone, but not rod, terminals in the outer plexiform layer (OPL) and in many synaptic terminals in the inner plexiform layer (IPL). SV2B was present only in the ribbon synapse-containing terminals of rod and cone photoreceptors and bipolar cells. SV2C was present in starburst amacrine cells, other conventional synapses in the IPL of unknown origin, and in presumptive interplexiform cell terminals in the INL and OPL. Each SV2 isoform was expressed in its distinct presynaptic terminals early and throughout postnatal development. In addition, SV2A was transiently expressed by developing horizontal cells. The unique distribution of each isoform suggests potentially distinct functions at different types of synapses, with SV2B having ribbon synapse-specific functions, and SV2C being important for the functions of starburst amacrine cells. Rod and cone terminals contain different complements of SV2 isoforms, indicating that ribbon synapses are not all identical. The early expression of SV2 isoforms prior to initiation of synapse formation suggests that they may have important synapse-specific roles during synaptogenesis.

Synaptic Vesicle Protein 2B Is Expressed in Podocyte, and Its Expression Is Altered in Proteinuric Glomeruli

“…Because Rab proteins confer specificity to vesicles, these results indicate that "synaptic vesicle-like vesicles" function in trafficking and secretion in general tissues. Some recent studies reported that SV2B plays an important role in maintaining tissue-specific function (15)(16)(17)(18). The tissue-specific expression of SV2B suggests that SV2B plays a role in forming the tissuespecific structure.…”

“…SV2 is known to participate in the regulation of calcium-mediated synaptic transmission and to play a role in vesicle trafficking by binding to other cell surface proteins (13,14). Although SV2 originally was reported to be expressed specifically in the central nervous system, recent studies have shown that it also is distributed in other organs (15)(16)(17). Hayashi et al (18) reported that SV2B is expressed in the microvesicles of pinealocytes, which are rich in process terminals.…”

Synaptic vesicle dynamics in mouse rod bipolar cells

“…Whole mount preparations were incubated in primary antibody for 7 days at 4°C. Primary antibodies used were ➀ rabbit polyclonal antibody anti-protein kinase C (Calbiochem, San Diego, CA) at dilution 1:1000, as a marker of rod bipolar cells (Wang et al, 2003) and ➁ ribbon-specific mouse monoclonal antibody anti-CtBP2/ribeye, dilution 1:200 (BD Transduction Laboratories, San Jose, CA, 612044). For fluorescence labeling, cells were incubated with a mixture of Alexa-tagged antimouse (488 nM) and anti-rabbit (568 nM) IgG secondary antibodies (Molecular Probes, Eugene, OR, USA) at 1:1000 dilutions for 1hr at room temperature in a light-protected environment.…”

“…Synaptic ribbons were identified by immunostaining for CtBP2/ribeye, a structural element of the synaptic ribbon (Schmitz et al, 2000;tom Dieck et al, 2005), shown in green in Figures 1A, 1D, and 1G. Rod bipolar cells were identified by red labeling with an antibody directed against protein kinase C alpha (PKC-α) (Wang et al, 2003) in Figures 1B, 1E, and 1H. The merged images from PKC-α and CtBP2/ribeye double-labeled cells ( Figures 1C, 1F, and 1I) reveal that CtBP2 immunofluorescence (green) is prominent in the synaptic terminals of rod bipolar cells and in the inner plexiform layer of the retina (IPL), as expected.…”

Synaptic Ca2+in Darkness Is Lower in Rods than Cones, Causing Slower Tonic Release of Vesicles

“…Rods and cones have the same subtypes of exocytotic and endocytotic proteins, although there are differences in their relative abundance (Sherry and Heidelberger, 2005). Also, synaptic vesicle protein 2B is found in rods and not cones (Wang et al, 2003), but its function is unclear. Despite these differences, we find the same Ca 2ϩ dependence of release from rods and cones.…”