The phosphatidylinositol-transfer protein Nir3 promotes PI(4,5)P2 replenishment in response to TCR signaling during T cell development and survival

Wen Lu, Ynes A. Helou, Krishna Shrinivas, Jen Liou, Byron B. Au-Yeung, Arthur Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C-γ (PLCγ1) represents a critical step in T cell antigen receptor (TCR) signaling and subsequent thymocyte and T cell responses. PIP2 replenishment following its depletion in the plasma membrane (PM) is dependent on delivery of its precursor phosphatidylinositol (PI) from the endoplasmic reticulum (ER) to the PM. We show that a PI transfer protein (PITP), Nir3 (Pitpnm2), promotes PIP2 replenishment following TCR stimulation and is important for T cell development. In Nir3–/– T lineage cells, the PIP2 replenishment following TCR stimulation is slower. Nir3 deficiency attenuates calcium mobilization in double-positive (DP) thymocytes in response to weak TCR stimulation. This impaired TCR signaling leads to attenuated thymocyte development at TCRβ selection and positive selection as well as diminished mature T cell fitness in Nir3–/– mice. This study highlights the importance of PIP2 replenishment mediated by PITPs at ER-PM junctions during TCR signaling.

Original languageEnglish (US)
Pages (from-to)136-147
Number of pages12
JournalNature Immunology
Volume24
Issue number1
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'The phosphatidylinositol-transfer protein Nir3 promotes PI(4,5)P2 replenishment in response to TCR signaling during T cell development and survival'. Together they form a unique fingerprint.

Cite this