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

Alejandro Vila,Zhijing Zhang,Christophe P Ribelayga,Abirami Santhanam,John O’Brien,Eyad Shihabeddin

doi:10.3389/fncel.2021.667046

Abstract

Synaptic signaling complexes are held together by scaffold proteins, each of which is selectively capable of interacting with a number of other proteins. In previous studies of rabbit retina, we found Synapse-Associated Protein-102 (SAP102) and Channel Associated Protein of Synapse-110 (Chapsyn110) selectively localized in the tips of horizontal cell processes at contacts with rod and cone photoreceptors, along with several interacting ion channels. We have examined the equivalent suites of proteins in mouse retina and found similarities and differences. In the mouse retina we identified Chapsyn110 as the scaffold selectively localized in the tips of horizontal cells contacting photoreceptors, with Sap102 more diffusely present. As in rabbit, the inward rectifier potassium channel Kir2.1 was present with Chapsyn110 on the tips of horizontal cell dendrites within photoreceptor invaginations, where it could provide a hyperpolarization-activated current that could contribute to ephaptic signaling in the photoreceptor synapses. Pannexin 1 and Pannexin 2, thought to play a role in ephaptic and/or pH mediated signaling, were present in the outer plexiform layer, but likely not in the horizontal cells. Polyamines regulate many ion channels and control the degree of rectification of Kir2.1 by imposing a voltage-dependent block. During the day polyamine immunolabeling was unexpectedly high in photoreceptor terminals compared to other areas of the retina. This content was significantly lower at night, when polyamine content was predominantly in Müller glia, indicating daily rhythms of polyamine content. Both rod and cone terminals displayed the same rhythm. While polyamine content was not prominent in horizontal cells, if polyamines are released, they may regulate the activity of Kir2.1 channels located in the tips of HCs. The rhythmic change in polyamine content of photoreceptor terminals suggests that a daily rhythm tunes the behavior of suites of ion channels within the photoreceptor synapses.

Highlights

The visual world presents an enormous diversity of experience across intensity, spatial and temporal scales, presenting great challenges to extract useful information
We have examined the distribution of membrane-associated guanylate kinase (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)
We have previously examined the distribution of synaptic scaffold proteins in rabbit photoreceptor synapses (Vila et al, 2017), finding that the membrane-associated guanylate kinase (MAGUK) scaffold proteins Synapse-Associated Protein 102 (SAP102 or Dlg3) and Channel Associated Protein of Synapse110 (Chapsyn110 or Dlg2; known as PSD93) assembled a complex of ion channels in the tips of horizontal cells

Summary

Introduction

The visual world presents an enormous diversity of experience across intensity, spatial and temporal scales, presenting great challenges to extract useful information. Two mechanisms have emerged that have gained substantial experimental support: a proton-mediated mechanism in which modulation of the local pH within the photoreceptor synapse alters the degree of inhibition of the voltage-gated calcium channel (Hirasawa and Kaneko, 2003; Vessey et al, 2005; Vroman et al, 2014; Wang et al, 2014; Warren et al, 2016a; Grove et al, 2019), and an ephaptic mechanism in which ion channels in horizontal cell processes support electrical currents through the extracellular space of the invaginating synapse that create a voltage drop sensed by the photoreceptor voltage-gated calcium channel (Kamermans et al, 2001; Fahrenfort et al, 2005; Klaassen et al, 2011) Both cone and rod photoreceptors experience the same type of feedback (Thoreson et al, 2008; Babai and Thoreson, 2009), but the diversity of mechanisms reported from different groups of vertebrates and widely differing experimental measures of the weighting and even presence of the two core mechanisms in different species (Vroman et al, 2014; Warren et al, 2016b; Grove et al, 2019; Barnes et al, 2020) make it unclear how widely the mechanisms are conserved

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Conclusion