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

Qian Gao, Junfeng Zhang, Xiumei Wang, Ying Liu, Rongqiao He, Xingfeng Liu, Fei Wang, Jing Feng, Dongling Yang, Zhaoqing Wang (), Anming Meng () and Xiyun Yan ()
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Qian Gao: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences
Junfeng Zhang: State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, Tsinghua University
Xiumei Wang: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences
Ying Liu: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences
Rongqiao He: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences
Xingfeng Liu: State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, Tsinghua University
Fei Wang: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences
Jing Feng: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences
Dongling Yang: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences
Zhaoqing Wang: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences
Anming Meng: State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, Tsinghua University
Xiyun Yan: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15279

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