<scp>LRRTM4</scp> is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

Agosto, Melina A.; Wensel, Theodore G.

doi:10.1002/cne.24944

Cited by 13 publications

(16 citation statements)

References 65 publications

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“…mGluR6 WT and mutant constructs with C-terminal EGFP fusions were expressed in ON-BCs in WT CD1 mice by in vivo electroporation ( 23 ). WT mGluR6-EGFP colocalized with dendritic tip puncta in the OPL, as expected ( 24 ). CT deletions, including removal of nearly the entire region following the last transmembrane helix, did not affect dendritic tip localization at the resolution of confocal microscopy.…”

Section: Resultssupporting

confidence: 84%

“…The localization of all LBD mutants in somas was similar to that of somatic TRPM1 (Fig. 6A), which was previously shown to be mostly localized to the ER (24). Furthermore, Δ24-58 and Δ24-189 were partially colocalized with the ER marker BiP (Fig.…”

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 73%

“…In theory, the ability of mutants to mediate synaptic transmission could also be assayed by introducing them into the nob3 background. However, transfection of BCs by electroporation of plasmid DNA is relatively inefficient and typically occurs in patches ( 23 , 24 , 43 ). While sometimes advantageous for imaging studies, the sparse transfection would likely make it challenging to observe phenotypes by electroretinogram recordings or behavioral experiments.…”

Section: Discussionmentioning

confidence: 99%

“…WT or mutant mGluR6-GGGSGGG-EGFP, or DsRed, was cloned into pGrm6P. pCDNA3.1 with the extracellular domain of mouse ELFN1 (a.a. 1–418) or mouse LRRTM4 (a.a. 1–425) fused to human Fc was described previously ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

“…Subretinal injection and electroporation were performed at P0 essentially as described ( 23 , 24 , 62 ). Plasmid DNA was prepared using a Qiagen maxiprep kit and dissolved in water.…”

Section: Methodsmentioning

confidence: 99%

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The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells

Agosto

Adeosun

Kumar

et al. 2021

Journal of Biological Chemistry

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Signals from retinal photoreceptors are processed in two parallel channels—the ON channel responds to light increments, while the OFF channel responds to light decrements. The ON pathway is mediated by ON type bipolar cells (BCs), which receive glutamatergic synaptic input from photoreceptors via a G-protein-coupled receptor signaling cascade. The metabotropic glutamate receptor mGluR6 is located at the dendritic tips of all ON-BCs and is required for synaptic transmission. Thus, it is critically important for delivery of information from photoreceptors into the ON pathway. In addition to detecting glutamate, mGluR6 participates in interactions with other postsynaptic proteins, as well as trans-synaptic interactions with presynaptic ELFN proteins. Mechanisms of mGluR6 synaptic targeting and functional interaction with other synaptic proteins are unknown. Here, we show that multiple regions in the mGluR6 ligand-binding domain are necessary for both synaptic localization in BCs and ELFN1 binding in vitro . However, these regions were not required for plasma membrane localization in heterologous cells, indicating that secretory trafficking and synaptic localization are controlled by different mechanisms. In contrast, the mGluR6 C-terminus was dispensable for synaptic localization. In mGluR6 null mice, localization of the postsynaptic channel protein TRPM1 was compromised. Introducing WT mGluR6 rescued TRPM1 localization, while a C-terminal deletion mutant had significantly reduced rescue ability. We propose a model in which trans-synaptic ELFN1 binding is necessary for mGluR6 postsynaptic localization, whereas the C-terminus has a role in mediating TRPM1 trafficking. These findings reveal different sequence determinants of the multifunctional roles of mGluR6 in ON-BCs.

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Section: Resultssupporting

confidence: 84%

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Subretinal injection and electroporation were performed at P0 essentially as described ( 23 , 24 , 62 ). Plasmid DNA was prepared using a Qiagen maxiprep kit and dissolved in water.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells

Agosto

Adeosun

Kumar

et al. 2021

Journal of Biological Chemistry

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CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

Melrose

2024

J of Neuroscience Research

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Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space‐filling, cell supportive, stabilizing structure maintaining tissue compartments, ionic microenvironments, and microgradients that regulate neuronal activity and maintain the neuron in an optimal ionic microenvironment. The CNS/PNS contains a high glycosaminoglycan content (60% hyaluronan, HA) and a diverse range of stabilizing PGs. Immobilization of HA in brain tissues by HA interactive hyalectan PGs preserves tissue hydration and neuronal activity, a paucity of HA in brain tissues results in a pro‐convulsant epileptic phenotype. Diverse CS, KS, and HSPGs stabilize the blood–brain barrier and neurovascular unit, provide smart gel neurotransmitter neuron vesicle storage and delivery, organize the neuromuscular junction basement membrane, and provide motor neuron synaptic plasticity, and photoreceptor and neuron synaptic functions. PG‐HA networks maintain ionic fluxes and microgradients and tissue compartments that contribute to membrane polarization dynamics essential to neuronal activation and neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing to synaptic plasticity, memory, and cognitive learning. Sialoglycoprotein associated with cones and rods (SPACRCAN), an HA binding CSPG, stabilizes the inter‐photoreceptor ECM. HSPGs pikachurin and eyes shut stabilize the photoreceptor synapse aiding in phototransduction and neurotransduction with retinal bipolar neurons crucial to visual acuity. This is achieved through Laminin G motifs in pikachurin, eyes shut, and neurexins that interact with the dystroglycan–cytoskeleton–ECM‐stabilizing synaptic interconnections, neuronal interactive specificity, and co‐ordination of regulatory action potentials in neural networks.

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LRIT3 expression in cone photoreceptors restores post-synaptic bipolar cell signalplex assembly and partial function in Lrit3 mice

Gregg¹,

Hasan²,

Borghuis³

2023

iScience

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LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

Cited by 13 publications

References 65 publications

The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells

The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

LRIT3 expression in cone photoreceptors restores post-synaptic bipolar cell signalplex assembly and partial function in Lrit3 mice

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