Cargando…

Regulation of dendrite morphology and excitatory synapse formation by zDHHC15

Protein palmitoylation is the most common post-translational lipid modification in the brain and is mediated by a family of 24 zDHHC enzymes. There has been growing interest in zDHHCs due to mounting evidence that these enzymes play key roles in the development and function of neuronal connections,...

Descripción completa

Detalles Bibliográficos
Autores principales: Shah, Bhavin S., Shimell, Jordan J., Bamji, Shernaz X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6633394/
https://www.ncbi.nlm.nih.gov/pubmed/31189538
http://dx.doi.org/10.1242/jcs.230052
_version_ 1783435720777531392
author Shah, Bhavin S.
Shimell, Jordan J.
Bamji, Shernaz X.
author_facet Shah, Bhavin S.
Shimell, Jordan J.
Bamji, Shernaz X.
author_sort Shah, Bhavin S.
collection PubMed
description Protein palmitoylation is the most common post-translational lipid modification in the brain and is mediated by a family of 24 zDHHC enzymes. There has been growing interest in zDHHCs due to mounting evidence that these enzymes play key roles in the development and function of neuronal connections, and the fact that a number of zDHHCs have been associated with neurodevelopmental and neurodegenerative diseases. Loss-of-function variants in several zDHHCs, including zDHHC15, have been identified in patients with intellectual disabilities; however, the function of zDHHC15 in the brain has not been well studied. Here, we demonstrate that knocking down zDHHC15 in primary rat hippocampal cultures reduces dendritic outgrowth and arborization, as well as spine maturation. Moreover, knockdown of zDHHC15 reduces palmitoylation of PSD-95 and its trafficking into dendrites, resulting in an overall decrease in the density of excitatory synapses being formed onto mutant cells.
format Online
Article
Text
id pubmed-6633394
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher The Company of Biologists Ltd
record_format MEDLINE/PubMed
spelling pubmed-66333942019-08-01 Regulation of dendrite morphology and excitatory synapse formation by zDHHC15 Shah, Bhavin S. Shimell, Jordan J. Bamji, Shernaz X. J Cell Sci Short Report Protein palmitoylation is the most common post-translational lipid modification in the brain and is mediated by a family of 24 zDHHC enzymes. There has been growing interest in zDHHCs due to mounting evidence that these enzymes play key roles in the development and function of neuronal connections, and the fact that a number of zDHHCs have been associated with neurodevelopmental and neurodegenerative diseases. Loss-of-function variants in several zDHHCs, including zDHHC15, have been identified in patients with intellectual disabilities; however, the function of zDHHC15 in the brain has not been well studied. Here, we demonstrate that knocking down zDHHC15 in primary rat hippocampal cultures reduces dendritic outgrowth and arborization, as well as spine maturation. Moreover, knockdown of zDHHC15 reduces palmitoylation of PSD-95 and its trafficking into dendrites, resulting in an overall decrease in the density of excitatory synapses being formed onto mutant cells. The Company of Biologists Ltd 2019-07-01 2019-07-05 /pmc/articles/PMC6633394/ /pubmed/31189538 http://dx.doi.org/10.1242/jcs.230052 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Short Report
Shah, Bhavin S.
Shimell, Jordan J.
Bamji, Shernaz X.
Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title_full Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title_fullStr Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title_full_unstemmed Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title_short Regulation of dendrite morphology and excitatory synapse formation by zDHHC15
title_sort regulation of dendrite morphology and excitatory synapse formation by zdhhc15
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6633394/
https://www.ncbi.nlm.nih.gov/pubmed/31189538
http://dx.doi.org/10.1242/jcs.230052
work_keys_str_mv AT shahbhavins regulationofdendritemorphologyandexcitatorysynapseformationbyzdhhc15
AT shimelljordanj regulationofdendritemorphologyandexcitatorysynapseformationbyzdhhc15
AT bamjishernazx regulationofdendritemorphologyandexcitatorysynapseformationbyzdhhc15