Cargando…

Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions

Doc2a and Doc2b are high-affinity calcium-binding proteins that interact with SNARE proteins and phospholipids. Experiments performed on cultured cells indicated that Doc2 proteins promote spontaneous vesicle fusion and asynchronous neurotransmitter release, regulate vesicle priming, mediate augment...

Descripción completa

Detalles Bibliográficos
Autores principales: Khan, Mehak M, Regehr, Wade G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190354/
https://www.ncbi.nlm.nih.gov/pubmed/32347796
http://dx.doi.org/10.7554/eLife.55165
_version_ 1783527671593959424
author Khan, Mehak M
Regehr, Wade G
author_facet Khan, Mehak M
Regehr, Wade G
author_sort Khan, Mehak M
collection PubMed
description Doc2a and Doc2b are high-affinity calcium-binding proteins that interact with SNARE proteins and phospholipids. Experiments performed on cultured cells indicated that Doc2 proteins promote spontaneous vesicle fusion and asynchronous neurotransmitter release, regulate vesicle priming, mediate augmentation, and regulate transmission during sustained activity. Here, we assess the role of Doc2 proteins in synaptic transmission under physiological conditions at mature synapses made by Purkinje cells onto neurons in the deep cerebellar nuclei (PC to DCN synapses). PCs express Doc2b but not Doc2a. Surprisingly, spontaneous neurotransmitter release, synaptic strength, the time course of evoked release, responses evoked by sustained high-frequency stimulation, and short-term plasticity were normal in Doc2b KO mice. Thus, in stark contrast to numerous functions previously proposed for Doc2, here we find that Doc2b removal does not influence transmission at PC-to-DCN synapses, indicating that conclusions based on studies of Doc2b in cultured cells do not necessarily generalize to mature synapses under physiological conditions.
format Online
Article
Text
id pubmed-7190354
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-71903542020-05-01 Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions Khan, Mehak M Regehr, Wade G eLife Neuroscience Doc2a and Doc2b are high-affinity calcium-binding proteins that interact with SNARE proteins and phospholipids. Experiments performed on cultured cells indicated that Doc2 proteins promote spontaneous vesicle fusion and asynchronous neurotransmitter release, regulate vesicle priming, mediate augmentation, and regulate transmission during sustained activity. Here, we assess the role of Doc2 proteins in synaptic transmission under physiological conditions at mature synapses made by Purkinje cells onto neurons in the deep cerebellar nuclei (PC to DCN synapses). PCs express Doc2b but not Doc2a. Surprisingly, spontaneous neurotransmitter release, synaptic strength, the time course of evoked release, responses evoked by sustained high-frequency stimulation, and short-term plasticity were normal in Doc2b KO mice. Thus, in stark contrast to numerous functions previously proposed for Doc2, here we find that Doc2b removal does not influence transmission at PC-to-DCN synapses, indicating that conclusions based on studies of Doc2b in cultured cells do not necessarily generalize to mature synapses under physiological conditions. eLife Sciences Publications, Ltd 2020-04-29 /pmc/articles/PMC7190354/ /pubmed/32347796 http://dx.doi.org/10.7554/eLife.55165 Text en © 2020, Khan and Regehr http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Khan, Mehak M
Regehr, Wade G
Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title_full Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title_fullStr Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title_full_unstemmed Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title_short Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions
title_sort loss of doc2b does not influence transmission at purkinje cell to deep nuclei synapses under physiological conditions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190354/
https://www.ncbi.nlm.nih.gov/pubmed/32347796
http://dx.doi.org/10.7554/eLife.55165
work_keys_str_mv AT khanmehakm lossofdoc2bdoesnotinfluencetransmissionatpurkinjecelltodeepnucleisynapsesunderphysiologicalconditions
AT regehrwadeg lossofdoc2bdoesnotinfluencetransmissionatpurkinjecelltodeepnucleisynapsesunderphysiologicalconditions