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Updated: Jun 9, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
E-Syt1 recruits PI4KA to endoplasmic reticulum-plasma membrane junctions to enhance PI4P synthesis
Chunfang Tong1, Ranran Mao1,2, Dou Wang1
1Laboratory of Integrative Physiology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
None:
Phosphatidylinositol-4-phosphate (PI4P) is a low-abundance membrane lipid that plays crucial roles in lipid exchange and homeostasis, signal transduction, and vesicle trafficking. PI4KA, a type III phosphatidylinositol 4-kinase, catalyzes PI4P synthesis at the plasma membrane (PM). However, the mechanism by which cytoplasmic PI4KA is recruited to the PM to regulate PI4P levels in response to extracellular and intracellular signals remains unclear. We found that PI4KA is tightly associated with membranous organelles, including the endoplasmic reticulum (ER). In response to Ca2+, the membrane tethering protein extended synaptotagmin 1 (E-Syt1) recruits ER-localized PI4KA to ER-PM junctions, facilitating its PM recruitment and the assembly of the enzyme complex. In hippocampal neurons undergoing synaptic potentiation, neuronal activity-induced PM localization of PI4KA and PM PI4P synthesis also rely on E-Syt1 function. Thus, E-Syt1-mediated PI4KA localization to ER-PM junctions serves as a critical mechanism by which Ca2+ signaling regulates lipid metabolism at the PM.
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