Membrane‐associated guanylate kinase scaffolds organize a horizontal cell synaptic complex restricted to invaginating contacts with photoreceptors

Abstract

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in the tips of B-type horizontal cell processes where they contact cone and rod photoreceptors. We further identified some known SAP102 binding partners, kainate receptor GluR6/7 and inward rectifier potassium channel Kir2.1, closely associated with SAP102 in photoreceptor invaginations. The kainate receptor occupies a position distinct from that of the majority of AMPA receptors that dominate the horizontal cell post-synaptic response. GluR6/7 and Kir2.1 presumably are involved in synaptic processes that govern cell-to-cell communication, and could both contribute in different ways to synaptic currents that mediate feedback signaling. Notably, we failed to find evidence for the presence of Cx57 or Cx59 that might be involved in ephaptic feedback signaling in this complex. The presence of SAP102 and its binding partners in both cone and rod invaginating synapses suggests that whatever mechanism is supported by this protein complex is present in both types of photoreceptors.

JNK activity modulates postsynaptic scaffold protein SAP102 and kainate receptor dynamics in dendritic spines

“…As expected, this cytosolic region, which harbours a PDZ-binding motif at its distal C-terminus, also interacts with SAP102 via classical ligand-PDZ domain interactions that rely on the most C-terminal residues (see Supplementary Fig. S4; see also [30][31][32] ). Interestingly, the presence of the wild-type GluK2 cytoplasmic region strengthens the interaction between SAP102 and the regulatory protein JNK3: when the full-length GluK2 C-terminus is expressed together with SAP102 and JNK3, the binding of JNK3 to SAP102 is clear, whereas when we delete the PDZ-binding motif of GluK2, the interaction between JNK3 and SAP102 is comparably weak (see Fig.…”

Global epigenetic analysis of BDNF Val66Met mice hippocampus reveals changes in dendrite and spine remodeling genes

“…In this network, Creb1 is connected to two gene clusters. One is formed by subunits of the glutamate ionotropic receptor for kainate (Grik2, Grik5) and their associated interactors Neto2 and Dlg3 (Vila et al, ; Zhang et al, ). Notably, Grik2 has been associated with mood disorders in genetic studies and lower levels of Grik2 transcript have been found in hippocampus of bipolar patients (Cosgrove et al, ; de Sousa et al, ).…”

“…In this network, Creb1 is connected to two gene clusters. One is formed by subunits of the glutamate ionotropic receptor for kainate (Grik2, Grik5) and their associated interactors Neto2 and Dlg3 (Vila et al, 2017;Zhang et al, 2009).…”

Synaptic Scaffolds, Ion Channels and Polyamines in Mouse Photoreceptor Synapses: Anatomy of a Signaling Complex

“…Indeed, localization of several proteins to horizontal cells processes within the invaginating synapses of photoreceptors has been taken as important evidence of the existence of proposed feedback mechanisms ( Kamermans et al, 2001 ; Prochnow et al, 2009 ; Grove et al, 2019 ). In an earlier study, we have examined the distribution of MAGUK scaffold proteins that may anchor ion channels and other proteins in strategic locations that would allow them to be involved in horizontal cell feedback signaling in the rabbit retina ( Vila et al, 2017 ). This study identified the scaffolds SAP102 and Chapsyn110 to be localized selectively in the tips of horizontal cell processes where they make invaginating contacts with rod and cone photoreceptors.…”

“…The inward rectifier potassium channel Kir2.1 generates a hyperpolarization-activated potassium conductance that, in principle, could provide an ephaptic feedback signal within the photoreceptor invaginating synapses ( Vila et al, 2017 ). Rectification of inward rectifier potassium channels results from voltage-dependent channel block by intracellular polyamines ( Williams, 1997 ; Baronas and Kurata, 2014 ).…”