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TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

Publication ,  Journal Article
Shan, KZ; Le, T; Liang, P; Dong, P; Lowry, AJ; Kremmyda, P; Claesson-Welsh, L; Yang, H
Published in: J Cell Sci
July 15, 2024

TMEM16F (also known as ANO6), a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes, such as blood coagulation, neurodegeneration, cell-cell fusion and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight the role of intracellular signaling by TMEM16F in endothelial cells but also open new avenues for exploring the regulatory mechanisms for membrane lipid asymmetry and their implications in disease pathogenesis.

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Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

July 15, 2024

Volume

137

Issue

14

Location

England

Related Subject Headings

  • src-Family Kinases
  • Signal Transduction
  • Phosphorylation
  • Phospholipid Transfer Proteins
  • Neovascularization, Physiologic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Human Umbilical Vein Endothelial Cells
 

Citation

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Shan, K. Z., Le, T., Liang, P., Dong, P., Lowry, A. J., Kremmyda, P., … Yang, H. (2024). TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling. J Cell Sci, 137(14). https://doi.org/10.1242/jcs.261566
Shan, Ke Zoe, Trieu Le, Pengfei Liang, Ping Dong, Augustus J. Lowry, Polina Kremmyda, Lena Claesson-Welsh, and Huanghe Yang. “TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.J Cell Sci 137, no. 14 (July 15, 2024). https://doi.org/10.1242/jcs.261566.
Shan KZ, Le T, Liang P, Dong P, Lowry AJ, Kremmyda P, et al. TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling. J Cell Sci. 2024 Jul 15;137(14).
Shan, Ke Zoe, et al. “TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.J Cell Sci, vol. 137, no. 14, July 2024. Pubmed, doi:10.1242/jcs.261566.
Shan KZ, Le T, Liang P, Dong P, Lowry AJ, Kremmyda P, Claesson-Welsh L, Yang H. TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling. J Cell Sci. 2024 Jul 15;137(14).
Journal cover image

Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

July 15, 2024

Volume

137

Issue

14

Location

England

Related Subject Headings

  • src-Family Kinases
  • Signal Transduction
  • Phosphorylation
  • Phospholipid Transfer Proteins
  • Neovascularization, Physiologic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Human Umbilical Vein Endothelial Cells