PLD1 Negatively Regulates Dendritic Branching.
Neurons have characteristic dendritic arborization patterns that contribute to information processing. One essential component of dendritic arborization is the formation of a specific number of branches. Although intracellular pathways promoting dendritic growth and branching are being elucidated, the mechanisms that negatively regulate the branching of dendrites remain enigmatic. In this study, using gain-of-function and loss-of-function studies, we show that phospholipase D1 (PLD1) acts as a negative regulator of dendritic branching in cultured hippocampal neurons from embryonic day 18 rat embryos. Overexpression of wild-type PLD1 (WT-PLD1) decreases the complexity of dendrites, whereas knockdown or inhibition of PLD1 increases dendritic branching. We further demonstrated that PLD1 acts downstream of RhoA, one of the small Rho GTPases, to suppress dendritic branching. The restriction of dendritic branching by constitutively active RhoA (V14-RhoA) can be partially rescued by knockdown of PLD1. Moreover, the inhibition of dendritic branching by V14-RhoA and WT-PLD1 can be partially ameliorated by reducing the level of phosphatidic acid (PA), which is the enzymatic product of PLD1. Together, these results suggest that RhoA-PLD1-PA may represent a novel signaling pathway in the restriction of dendritic branching and may thus provide insight into the mechanisms of dendritic morphogenesis.
Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Yan-Bing
YB
Zhu
Kai
K
Kang
Ying
Y
Zhang
Cai
C
Qi
Gang
G
Li
Dong-Min
DM
Yin
Yun
Y
Wang
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D047468:Immunoprecipitation; D008297:Male; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000502:physiology*; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D010712:Phosphatidic Acids; D034741:RNA, Small Interfering; D004247:DNA; D010739:Phospholipase D; C106801:phospholipase D1; D020742:rhoA GTP-Binding Protein