Trafficking and Activity of Glutamate and GABA Receptors: Regulation by Cell Adhesion Molecules

Keable, Ryan; Leshchyns’ka, Iryna; Sytnyk, Vladimir

doi:10.1177/1073858420921117

Cited by 14 publications

(9 citation statements)

References 194 publications

(289 reference statements)

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“…Distinct molecular events have been identified for the mechanism and function of CAMs heterooligomerization. The ER exit of the multimeric neuronal synaptic N-Methyl-D-aspartic/aspartate receptor (NMDA) requires two NCAM-subunits to mask its ER retention signal and enhance the PM delivery of the NMDA 51 , 52 . NCAM is also known to modulate the synaptic trafficking of the NMDA receptor 51 , 52 .…”

Section: Discussionmentioning

confidence: 99%

“…The ER exit of the multimeric neuronal synaptic N-Methyl-D-aspartic/aspartate receptor (NMDA) requires two NCAM-subunits to mask its ER retention signal and enhance the PM delivery of the NMDA 51 , 52 . NCAM is also known to modulate the synaptic trafficking of the NMDA receptor 51 , 52 . The Ig-domain type CAMs neuroplastin and basigin interact with the PM Ca 2+ -ATPases (PMCA) 1–4 subunits and facilitate the PMCA-complex delivery to the cell surface independently of their Ig domains.…”

Section: Discussionmentioning

confidence: 99%

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Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

Isenmann

López-Hernández

et al. 2021

Sci Rep

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The significance of crosstalks among constituents of plasma membrane protein clusters/complexes in cellular proteostasis and protein quality control (PQC) remains incompletely understood. Examining the glial (enriched) cell adhesion molecule (CAM), we demonstrate its chaperone-like role in the biosynthetic processing of the megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1)-heteromeric regulatory membrane protein complex, as well as the function of the GlialCAM/MLC1 signalling complex. We show that in the absence of GlialCAM, newly synthesized MLC1 molecules remain unfolded and are susceptible to polyubiquitination-dependent proteasomal degradation at the endoplasmic reticulum. At the plasma membrane, GlialCAM regulates the diffusional partitioning and endocytic dynamics of cluster members, including the ClC-2 chloride channel and MLC1. Impaired folding and/or expression of GlialCAM or MLC1 in the presence of diseases causing mutations, as well as plasma membrane tethering compromise the functional expression of the cluster, leading to compromised endo-lysosomal organellar identity. In addition, the enlarged endo-lysosomal compartments display accelerated acidification, ubiquitinated cargo-sorting and impaired endosomal recycling. Jointly, these observations indicate an essential and previously unrecognized role for CAM, where GliaCAM functions as a PQC factor for the MLC1 signalling complex biogenesis and possess a permissive role in the membrane dynamic and cargo sorting functions with implications in modulations of receptor signalling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

Isenmann

López-Hernández

et al. 2021

Sci Rep

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“…Finally, the up-regulation of glutamate receptor GRIN3A on GB surfaces compared to Ti surfaces may explain the increased mineralization observed on these surfaces in vitro [ 7 ]. Glutamate signaling was indeed shown to increase osteoblast differentiation and function [ 39 ], and the up-regulation of GRIN3A may partly be a result of differential cell adhesion to the different surface roughness of the two materials [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

Shah

Dunning

Gartland

et al. 2021

IJMS

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Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co2+ and Cr3+ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co2+:Cr3+ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.

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“…The connectome of neuronal ensembles is orchestrated by neurite guidance, axonal and dendritic branching, synaptogenesis, and synaptic plasticity (Mrsic-Flogel and Bonhoeffer, 2012 ; Rajani et al, 2020 ; Rubio, 2020 ). The assembly of specific neuronal circuits depends on the expression of complementary molecular programs in presynaptic and postsynaptic neurons (Keable et al, 2020 ). Proteins are synthesized locally in different subcellular compartments such as dendritic shafts and spines, triggered by molecular signals such as neurotrophins, brain-derived neurotrophic factor, metabotropic glutamate receptor agonists, or by electrical stimulation (Ribeiro et al, 2019 ; Wu et al, 2019 ).…”

Section: Biologically Motivated Backgroundmentioning

confidence: 99%

Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility

et al. 2022

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Neuromorphic computer models are used to explain sensory perceptions. Auditory models generate cochleagrams, which resemble the spike distributions in the auditory nerve. Neuron ensembles along the auditory pathway transform sensory inputs step by step and at the end pitch is represented in auditory categorical spaces. In two previous articles in the series on periodicity pitch perception an extended auditory model had been successfully used for explaining periodicity pitch proved for various musical instrument generated tones and sung vowels. In this third part in the series the focus is on octopus cells as they are central sensitivity elements in auditory cognition processes. A powerful numerical model had been devised, in which auditory nerve fibers (ANFs) spike events are the inputs, triggering the impulse responses of the octopus cells. Efficient algorithms are developed and demonstrated to explain the behavior of octopus cells with a focus on a simple event-based hardware implementation of a layer of octopus neurons. The main finding is, that an octopus' cell model in a local receptive field fine-tunes to a specific trajectory by a spike-timing-dependent plasticity (STDP) learning rule with synaptic pre-activation and the dendritic back-propagating signal as post condition. Successful learning explains away the teacher and there is thus no need for a temporally precise control of plasticity that distinguishes between learning and retrieval phases. Pitch learning is cascaded: At first octopus cells respond individually by self-adjustment to specific trajectories in their local receptive fields, then unions of octopus cells are collectively learned for pitch discrimination. Pitch estimation by inter-spike intervals is shown exemplary using two input scenarios: a simple sinus tone and a sung vowel. The model evaluation indicates an improvement in pitch estimation on a fixed time-scale.

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Trafficking and Activity of Glutamate and GABA Receptors: Regulation by Cell Adhesion Molecules

Cited by 14 publications

References 194 publications

Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility

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