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  • LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Nature communications (2021-01-30)
Huai-Bin Hu, Zeng-Qing Song, Guang-Ping Song, Sen Li, Hai-Qing Tu, Min Wu, Yu-Cheng Zhang, Jin-Feng Yuan, Ting-Ting Li, Pei-Yao Li, Yu-Ling Xu, Xiao-Lin Shen, Qiu-Ying Han, Ai-Ling Li, Tao Zhou, Jerold Chun, Xue-Min Zhang, Hui-Yan Li
要旨

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

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