TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling

Area of Science:

• Cell Biology
• Molecular Biology
• Physiology

Background:

• TMEM16F (an octamin 6) is a Ca2+-activated lipid scramblase crucial for physiological and pathological processes.
• Its precise regulatory mechanisms in these processes remain largely unknown.

Purpose of the Study:

• To investigate the intracellular signaling function of TMEM16F in endothelial cell-mediated angiogenesis.
• To elucidate the molecular mechanisms underlying TMEM16F's role in vascular development.

Main Methods:

• Utilized a mouse model of developmental retinal angiogenesis.
• Performed in vitro angiogenic assays.
• Conducted biochemical analyses to assess Src kinase activity and VE-cadherin phosphorylation.

Main Results:

• TMEM16F deficiency impaired developmental retinal angiogenesis in mice and disrupted in vitro angiogenic processes.
• Absence of TMEM16F enhanced plasma membrane association of activated Src kinase.
• This led to increased VE-cadherin phosphorylation and downregulation, suppressing angiogenesis.

Conclusions:

• TMEM16F possesses a previously unrecognized intracellular signaling function in endothelial cells.
• TMEM16F regulates angiogenesis through modulation of Src kinase and VE-cadherin.
• Findings provide new avenues for understanding membrane lipid asymmetry and its role in disease pathogenesis.