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Distinct synaptic localization patterns of brefeldin A‐resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina
Author(s) -
Sakagami Hiroyuki,
Katsumata Osamu,
Hara Yoshinobu,
Tamaki Hideaki,
Watanabe Masahiko,
Harvey Robert J.,
Fukaya Masahiro
Publication year - 2013
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23206
Subject(s) - microbiology and biotechnology , inner plexiform layer , immunolabeling , immunoelectron microscopy , biology , outer plexiform layer , retina , postsynaptic potential , ampa receptor , guanine nucleotide exchange factor , neuroscience , glutamate receptor , gtpase , receptor , biochemistry , genetics , immunohistochemistry , antibody , immunology
The BRAG/IQSEC is a family of guanine nucleotide exchange factors for ADP ribosylation factors, small GTPases that regulate membrane trafficking and actin cytoskeleton, and comprises three structurally related members (BRAG1–3) generated from different genes. In the mouse retina, BRAG1 (also known as IQSEC2) was previously shown to localize at synaptic ribbons of photoreceptor terminals and to form a protein complex with RIBEYE. In this study, we examined the immunohistochemical localization of BRAG2 (IQSEC1) and BRAG3 (IQSEC3) in the adult mouse retina at the light and electron microscopic levels. In the outer plexiform layer, BRAG2 showed a punctate distribution in intimate association with dystrophin and β‐dystroglycan. Immunoelectron microscopic analysis revealed that BRAG2 localized at specific subcompartments of photoreceptor terminals in both rod spherules and cone pedicles. In the inner plexiform layer, immunolabeling for both BRAG2 and BRAG3 had a punctate appearance, suggestive of synaptic labeling. Double immunostaining demonstrated that BRAG2 colocalized preferentially with PSD‐95 and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate‐type glutamate receptors (AMPARs). By contrast, BRAG3 colocalized with gephyrin and a subpopulation of inhibitory synapses expressing glycine receptors or γ‐aminobutyric acid type A receptors (GABA A Rs). Immunoelectron microscopic analysis revealed that BRAG2 localized to postsynaptic processes at bipolar dyads, while BRAG3 localized to postsynaptic components at conventional synapses. These findings suggest that BRAG/IQSEC family members have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. J. Comp. Neurol. 521:860–876, 2013. © 2012 Wiley Periodicals, Inc.