Phosphatidylinositol 4, 5-bisphosphate homeostasis regulated by Nir2 and Nir3 proteins at endoplasmic reticulum-plasma membrane junctions

Chi Lun Chang, Jen Liou

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56 Scopus citations


Phosphatidylinositol (PI) 4, 5-bisphosphate (PIP<inf>2</inf>) at the plasma membrane (PM) constitutively controls many cellular functions, and its hydrolysis via receptor stimulation governs cell signaling. The PI transfer protein Nir2 is essential for replenishing PM PIP<inf>2</inf> following receptor-induced hydrolysis, but key mechanistic aspects of this process remain elusive. Here, we demonstrate that PI at the membrane of the endoplasmic reticulum (ER) is required for the rapid replenishment of PM PIP<inf>2</inf> mediated by Nir2. Nir2 detects PIP<inf>2</inf> hydrolysis and translocates to ER-PM junctions via binding to phosphatidic acid. With distinct phosphatidic acid binding abilities and PI transfer protein activities, Nir2 and its homolog Nir3 differentially regulate PIP<inf>2</inf> homeostasis in cells during intense receptor stimulation and in the resting state, respectively. Our study reveals that Nir2 and Nir3 work in tandemto achieve different levels of feedback based on the consumption of PM PIP<inf>2</inf> and function at ER-PM junctions to mediate nonvesicular lipid transport between the ER and the PM.

Original languageEnglish (US)
Pages (from-to)14289-14301
Number of pages13
JournalJournal of Biological Chemistry
Issue number23
Publication statusPublished - Jun 5 2015


ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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