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The signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis.

Nat Commun. 2017 Jun 07;8:15279
Qian Gao 1 , Junfeng Zhang 2 , Xiumei Wang 3 , Ying Liu 3 , Rongqiao He 4 , Xingfeng Liu 2 , Fei Wang 5 , Jing Feng 5 , Dongling Yang 5 , Zhaoqing Wang 5 , Anming Meng 2 , Xiyun Yan 1
Qian Gao 1 , Junfeng Zhang 2 , Xiumei Wang 3 , Ying Liu 3 , Rongqiao He 4 , Xingfeng Liu 2 , Fei Wang 5 , Jing Feng 5 , Dongling Yang 5 , Zhaoqing Wang 5 , Anming Meng 2 , Xiyun Yan 1
+ et al

[No authors listed]

Author information
  • 1 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
  • 3 State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
  • 5 Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

摘要


The apical-basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK. We find that MCAM-mediated vesicular trafficking towards FGF4, while generating a priority-grade transcriptional response of NFAT determines lumenogenesis. We demonstrate that MCAM plays indispensable roles in ciliogenesis through activating JNK independently of FGF signals. Furthermore, mcam-deficient zebrafish and Xenopus exhibit a global defect in left-right (LR) asymmetric establishment as a result of morphogenetic failure of their LR organizers. Therefore, MCAM coordination of AB polarity and PCP provides insight into the general mechanisms of morphogenesis.