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TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome
Canonical transient receptor potential channels (TRPC3) may play a pivotal role in the development and viability of dendritic arbor in Purkinje neurons. This is a novel postsynaptic channel for glutamatergic synaptic transmission. In the cerebellum, TRPC3 appears to regulate functions relating to mo...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899209/ https://www.ncbi.nlm.nih.gov/pubmed/35265671 http://dx.doi.org/10.3389/fmolb.2022.818682 |
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author | Aslam, Naveed Alvi, Farah |
author_facet | Aslam, Naveed Alvi, Farah |
author_sort | Aslam, Naveed |
collection | PubMed |
description | Canonical transient receptor potential channels (TRPC3) may play a pivotal role in the development and viability of dendritic arbor in Purkinje neurons. This is a novel postsynaptic channel for glutamatergic synaptic transmission. In the cerebellum, TRPC3 appears to regulate functions relating to motor coordination in a highly specific manner. Gain of TRPC3 function is linked to significant alterations in the density and connectivity of dendritic arbor in Purkinje neurons. TRPC3 signals downstream of class I metabotropic glutamate receptors (mGluR1). Moreover, diacylglycerol (DAG) can directly bind and activate TRPC3 molecules. Here, we investigate a key question: How can the activity of the TRPC3 channel be regulated in Purkinje neurons? We also explore how mGluR1 activation, Ca(2+) influx, and DAG homeostasis in Purkinje neurons can be linked to TRPC3 activity modulation. Through systems biology approach, we show that TRPC3 activity can be modulated by a Purkinje cell (PC)–specific local signalosome. The assembly of this signalosome is coordinated by DAG generation after mGluR1 activation. Our results also suggest that purinergic receptor activation leads to the spatial and temporal organization of the TRPC3 signaling module and integration of its key effector molecules such as DAG, PKCγ, DGKγ, and Ca(2+) into an organized local signalosome. This signaling machine can regulate the TRPC3 cycling between active, inactive, and desensitized states. Precise activity of the TRPC3 channel is essential for tightly regulating the Ca(2+) entry into PCs and thus the balance of lipid and Ca(2+) signaling in Purkinje neurons and hence their viability. Cell-type–specific understanding of mechanisms regulating TRPC3 channel activity could be key in identifying therapeutic targeting opportunities. |
format | Online Article Text |
id | pubmed-8899209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88992092022-03-08 TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome Aslam, Naveed Alvi, Farah Front Mol Biosci Molecular Biosciences Canonical transient receptor potential channels (TRPC3) may play a pivotal role in the development and viability of dendritic arbor in Purkinje neurons. This is a novel postsynaptic channel for glutamatergic synaptic transmission. In the cerebellum, TRPC3 appears to regulate functions relating to motor coordination in a highly specific manner. Gain of TRPC3 function is linked to significant alterations in the density and connectivity of dendritic arbor in Purkinje neurons. TRPC3 signals downstream of class I metabotropic glutamate receptors (mGluR1). Moreover, diacylglycerol (DAG) can directly bind and activate TRPC3 molecules. Here, we investigate a key question: How can the activity of the TRPC3 channel be regulated in Purkinje neurons? We also explore how mGluR1 activation, Ca(2+) influx, and DAG homeostasis in Purkinje neurons can be linked to TRPC3 activity modulation. Through systems biology approach, we show that TRPC3 activity can be modulated by a Purkinje cell (PC)–specific local signalosome. The assembly of this signalosome is coordinated by DAG generation after mGluR1 activation. Our results also suggest that purinergic receptor activation leads to the spatial and temporal organization of the TRPC3 signaling module and integration of its key effector molecules such as DAG, PKCγ, DGKγ, and Ca(2+) into an organized local signalosome. This signaling machine can regulate the TRPC3 cycling between active, inactive, and desensitized states. Precise activity of the TRPC3 channel is essential for tightly regulating the Ca(2+) entry into PCs and thus the balance of lipid and Ca(2+) signaling in Purkinje neurons and hence their viability. Cell-type–specific understanding of mechanisms regulating TRPC3 channel activity could be key in identifying therapeutic targeting opportunities. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8899209/ /pubmed/35265671 http://dx.doi.org/10.3389/fmolb.2022.818682 Text en Copyright © 2022 Aslam and Alvi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Aslam, Naveed Alvi, Farah TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title | TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title_full | TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title_fullStr | TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title_full_unstemmed | TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title_short | TRPC3 Channel Activity and Viability of Purkinje Neurons can be Regulated by a Local Signalosome |
title_sort | trpc3 channel activity and viability of purkinje neurons can be regulated by a local signalosome |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899209/ https://www.ncbi.nlm.nih.gov/pubmed/35265671 http://dx.doi.org/10.3389/fmolb.2022.818682 |
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