PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage

Abstract Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, th...

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Autores principales:	Li-Da Luo, Gang Li, Yun Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b2b2352d8904f289b2b0189925ce810
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spelling	oai:doaj.org-article:5b2b2352d8904f289b2b0189925ce8102021-12-02T12:32:06ZPLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage10.1038/s41598-017-06121-22045-2322https://doaj.org/article/5b2b2352d8904f289b2b0189925ce8102017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06121-2https://doaj.org/toc/2045-2322Abstract Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines. On the contrary, loss of function of PLD1, including overexpression of the catalytically-inactive PLD1 (PLD1ci) or knocking down PLD1 by siRNAs, leads to reduction in the spine density and the spine area. Moreover, we found that PLD1 promotes the dendritic spine development via regulating the membrane level of N-cadherin. Further studies showed that the regulation of surface N-cadherin by PLD1 is related with the cleavage of N-cadherin by a member of the disintegrin and metalloprotease family-ADAM10. Taking together, our results indicate a positive role of PLD1 in synaptogenesis by inhibiting the ADAM10 mediated N-cadherin cleavage and provide new therapeutic clues for some neurological diseases.Li-Da LuoGang LiYun WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li-Da Luo Gang Li Yun Wang PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
description	Abstract Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines. On the contrary, loss of function of PLD1, including overexpression of the catalytically-inactive PLD1 (PLD1ci) or knocking down PLD1 by siRNAs, leads to reduction in the spine density and the spine area. Moreover, we found that PLD1 promotes the dendritic spine development via regulating the membrane level of N-cadherin. Further studies showed that the regulation of surface N-cadherin by PLD1 is related with the cleavage of N-cadherin by a member of the disintegrin and metalloprotease family-ADAM10. Taking together, our results indicate a positive role of PLD1 in synaptogenesis by inhibiting the ADAM10 mediated N-cadherin cleavage and provide new therapeutic clues for some neurological diseases.
format	article
author	Li-Da Luo Gang Li Yun Wang
author_facet	Li-Da Luo Gang Li Yun Wang
author_sort	Li-Da Luo
title	PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
title_short	PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
title_full	PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
title_fullStr	PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
title_full_unstemmed	PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
title_sort	pld1 promotes dendritic spine development by inhibiting adam10-mediated n-cadherin cleavage
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5b2b2352d8904f289b2b0189925ce810
work_keys_str_mv	AT lidaluo pld1promotesdendriticspinedevelopmentbyinhibitingadam10mediatedncadherincleavage AT gangli pld1promotesdendriticspinedevelopmentbyinhibitingadam10mediatedncadherincleavage AT yunwang pld1promotesdendriticspinedevelopmentbyinhibitingadam10mediatedncadherincleavage
_version_	1718394158722318336

PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage

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