The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease

Martemyanov, Kirill A.; Sampath, Alapakkam P.

doi:10.1146/annurev-vision-102016-061338

Cited by 56 publications

(50 citation statements)

References 167 publications

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“…The mGluR6 pathway necessarily operates on the order of milliseconds, matching the kinetics of the rod light response (Berntson et al 2004). It is thought that signaling of the mGluR6 pathway relies on the direct interaction of Gbc and Ga o subunits with the TrpM1 channel (Martemyanov and Sampath 2017); in contrast, group I mGluRs require second-messenger systems to couple to their downstream targets. Additionally, the kinetics of mGluR1 activation/inactivation may be slower, integrating over longer times, rather than responding to rapid changes in transmitter release.…”

Section: The Mglur6-trpm1 Complex and Group I Mglurs In Rbc Dendritesmentioning

confidence: 99%

A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina

et al. 2018

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The canonical mGluR6‐Trpm1 pathway that generates the sign‐inverting signal between photoreceptors and ON bipolar cells has been well described. However, one type of ON bipolar cell, the rod bipolar cell (RBC), additionally is thought to express the group I mGluRs whose function is unknown. We examined the role of group I mGluRs in mouse RBCs and here provide evidence that it controls synaptic gain between rods and RBCs. In dark‐adapted conditions, the mGluR1 antagonists LY367385 and (RS)‐1‐Aminoindan‐1,5‐dicarboxylic acid, but not the mGluR5 antagonist 2‐Methyl‐6‐(phenylethynyl)pyridine hydrochloride reduced the light‐evoked responses in RBCs indicating that mGluR1, but not mGluR5, serves to potentiate RBC responses. Perturbing the downstream phospholipase C (PLC)‐protein kinase C (PKC) pathway by inhibiting PLC, tightly buffering intracellular Ca2+, or preventing its release from intracellular stores reduced the synaptic potentiation by mGluR1. The effect of mGluR1 activation was dependent upon adaptation state, strongly increasing the synaptic gain in dark‐, but not in light‐adapted retinas, or in the presence of a moderate background light, consistent with the idea that mGluR1 activation requires light‐dependent glutamate release from rods. Moreover, immunostaining revealed that protein kinase Cα (PKC α) is more strongly expressed in RBC dendrites in dark‐adapted conditions, revealing an additional mechanism behind the loss of mGluR1 potentiation. In light‐adapted conditions, exogenous activation of mGluR1 with the agonist 3,5‐Dihydroxyphenylglycine increased the mGluR6 currents in some RBCs and decreased it in others, suggesting an additional action of mGluR1 that is unmasked in the light‐adapted state. Elevating intracellular free Ca2+, consistently resulted in a decrease in synaptic gain. Our results provide evidence that mGluR1 controls the synaptic gain in RBCs.

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Section: The Mglur6-trpm1 Complex and Group I Mglurs In Rbc Dendritesmentioning

confidence: 99%

A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina

et al. 2018

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“…Suppression of the glutamate release by light leads to TRPM1 opening and requires rapid inactivation of Gao. This is achieved by the action of the GTPase activating protein (GAP) complex, which involves coordinated action of several proteins, including catalytic subunits RGS7 and RGS11 ( Martemyanov and Sampath, 2017 ; Vardi and Dhingra, 2014 ). The abundance and subcellular localization of the GAP complex have a major impact on the synaptic transmission of light signal from photoreceptors to ON-BC and tuning the circuits for daylight and dim vision ( Cao et al, 2009 ; Sarria et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors

et al. 2018

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SUMMARY Establishing synaptic contacts between neurons is paramount for nervous system function. This process involves transsynaptic interactions between a host of cell adhesion molecules that act in cooperation with the proteins of the extracellular matrix to specify uniquephysiological propertiesofindividual synaptic connections. However, understanding of the molecular mechanisms that generate functional diversity in an input-specific fashion is limited. In this study, we identify that major components of the extracellular matrix proteins present in the synaptic cleft—members oftheheparansulfateproteoglycan (HSPG) family—associate with the GPR158/179 group of orphan receptors. Using the mammalian retina as a model system, we demonstrate that the HSPG member Pikachurin, released by photoreceptors, recruits a key post-synaptic signaling complex of downstream ON-bipolar neurons in coordination with the presynaptic dystroglycan glycoprotein complex. We further demonstrate that this transsynaptic assembly plays an essential role in synaptic transmission of photoreceptor signals.

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“…The glutamate receptor, mGluR6, signals via the heterotrimeric G protein G o , which in turn gates a transduction channel by an unknown mechanism (for review, see Martemyanov and Sampath, 2017 ). Transient receptor potential melastatin-1 (TRPM1) is required for channel function ( Audo et al, 2009 ; Li et al, 2009 ; Morgans et al, 2009 ; Shen et al, 2009 ; Van Genderen et al, 2009 ; Koike et al, 2010b ), but it is not known if it is sufficient for formation of the G o -sensitive channel ( Lambert et al, 2011 ; Agosto et al, 2014 ; Schneider et al, 2015 ; Martemyanov and Sampath, 2017 ). In the dark, tonic release of glutamate activates mGluR6, keeping the channel closed; at light onset, decrease in glutamate release and deactivation of mGluR6 lead to channel opening and membrane depolarization.…”

Section: Introductionmentioning

confidence: 99%

A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells

Agosto

Anastassov

Robichaux

et al. 2018

eNeuro

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The chemical signal of light onset, a decrease in glutamate release from rod and cone photoreceptors, is processed by a postsynaptic G protein signaling cascade in ON-bipolar cells (BPCs). The metabotropic glutamate receptor mGluR6, along with other cascade elements, is localized synaptically at the BPC dendritic tips. The effector ion channel protein transient receptor potential melastatin-1 (TRPM1), in contrast, is located not only at the dendritic tips but also in BPC bodies and axons. Little is known about the intracellular localization of TRPM1, or its trafficking route to the dendritic tip plasma membrane. Recombinant TRPM1 expressed in mammalian cells colocalized with endoplasmic reticulum (ER) markers, with little or none detected at the plasma membrane. In mouse retina, somatic TRPM1 was similarly intracellular, and not at the plasma membrane. Labeling of ER membranes by expression of a fluorescent marker showed that in BPCs the ER extends into axons and dendrites, but not dendritic tips. In cell bodies, TRPM1 colocalized with the ER, and not with the Golgi apparatus. Fluorescence protease protection (FPP) assays with TRPM1-GFP fusions in heterologous cells revealed that the N and C termini are both accessible to the cytoplasm, consistent with the transmembrane domain topology of related TRP channels. These results indicate that the majority of TRPM1 is present in the ER, from which it can potentially be transported to the dendritic tips as needed for ON light responses. The excess of ER-resident TRPM1 relative to the amount needed at the dendritic tips suggests a potential new function for TRPM1 in the ER.

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The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease

Cited by 56 publications

References 167 publications

A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina

A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina

Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors

A Large Endoplasmic Reticulum-Resident Pool of TRPM1 in Retinal ON-Bipolar Cells

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