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LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.
Hu, Huai-Bin; Song, Zeng-Qing; Song, Guang-Ping; Li, Sen; Tu, Hai-Qing; Wu, Min; Zhang, Yu-Cheng; Yuan, Jin-Feng; Li, Ting-Ting; Li, Pei-Yao; Xu, Yu-Ling; Shen, Xiao-Lin; Han, Qiu-Ying; Li, Ai-Ling; Zhou, Tao; Chun, Jerold; Zhang, Xue-Min; Li, Hui-Yan.
Afiliación
  • Hu HB; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Song ZQ; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Song GP; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Li S; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Tu HQ; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Wu M; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Zhang YC; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Yuan JF; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Li TT; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Li PY; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Xu YL; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Shen XL; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Han QY; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Li AL; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Zhou T; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.
  • Chun J; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA.
  • Zhang XM; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China. zhangxuemin@cashq.ac.cn.
  • Li HY; State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China. hyli@ncba.ac.cn.
Nat Commun ; 12(1): 662, 2021 01 28.
Article en En | MEDLINE | ID: mdl-33510165
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lisofosfolípidos / Transducción de Señal / Cilios / Epitelio Pigmentado de la Retina / Neurogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lisofosfolípidos / Transducción de Señal / Cilios / Epitelio Pigmentado de la Retina / Neurogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido