Cargando…

5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation

The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor express...

Descripción completa

Detalles Bibliográficos
Autores principales: Samarajeewa, Anshula, Goldemann, Lolita, Vasefi, Maryam S., Ahmed, Nawaz, Gondora, Nyasha, Khanderia, Chandni, Mielke, John G., Beazely, Michael A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224134/
https://www.ncbi.nlm.nih.gov/pubmed/25426041
http://dx.doi.org/10.3389/fnbeh.2014.00391
_version_ 1782343313616011264
author Samarajeewa, Anshula
Goldemann, Lolita
Vasefi, Maryam S.
Ahmed, Nawaz
Gondora, Nyasha
Khanderia, Chandni
Mielke, John G.
Beazely, Michael A.
author_facet Samarajeewa, Anshula
Goldemann, Lolita
Vasefi, Maryam S.
Ahmed, Nawaz
Gondora, Nyasha
Khanderia, Chandni
Mielke, John G.
Beazely, Michael A.
author_sort Samarajeewa, Anshula
collection PubMed
description The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands.
format Online
Article
Text
id pubmed-4224134
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-42241342014-11-25 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation Samarajeewa, Anshula Goldemann, Lolita Vasefi, Maryam S. Ahmed, Nawaz Gondora, Nyasha Khanderia, Chandni Mielke, John G. Beazely, Michael A. Front Behav Neurosci Neuroscience The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands. Frontiers Media S.A. 2014-11-07 /pmc/articles/PMC4224134/ /pubmed/25426041 http://dx.doi.org/10.3389/fnbeh.2014.00391 Text en Copyright © 2014 Samarajeewa, Goldemann, Vasefi, Ahmed, Gondora, Khanderia, Mielke and Beazely. http://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) or licensor 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 Neuroscience
Samarajeewa, Anshula
Goldemann, Lolita
Vasefi, Maryam S.
Ahmed, Nawaz
Gondora, Nyasha
Khanderia, Chandni
Mielke, John G.
Beazely, Michael A.
5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title_full 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title_fullStr 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title_full_unstemmed 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title_short 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation
title_sort 5-ht7 receptor activation promotes an increase in trkb receptor expression and phosphorylation
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224134/
https://www.ncbi.nlm.nih.gov/pubmed/25426041
http://dx.doi.org/10.3389/fnbeh.2014.00391
work_keys_str_mv AT samarajeewaanshula 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT goldemannlolita 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT vasefimaryams 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT ahmednawaz 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT gondoranyasha 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT khanderiachandni 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT mielkejohng 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation
AT beazelymichaela 5ht7receptoractivationpromotesanincreaseintrkbreceptorexpressionandphosphorylation