TY - JOUR
T1 - Nir1 constitutively localizes at ER-PM junctions and promotes Nir2 recruitment for PIP2 homeostasis
AU - Quintanilla, Carlo Giovanni
AU - Lee, Wan Ru
AU - Liou, Jen
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Homeostatic regulation of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2) in receptor-stimulated cells is mediated by the lipid transfer protein Nir2. Nir2 is dynamically recruited to endoplasmic reticulum-plasma membrane (ER-PM) junctions to facilitate replenishment of PM PIP2 hydrolyzed during receptor-mediated signaling. However, our knowledge regarding the activation and sustainment of Nir2-mediated replenishment of PM PIP2 is limited. Here, we describe the functions of Nir1 as a positive regulator of Nir2 and PIP2 homeostasis. In contrast to the family proteins Nir2 and Nir3, Nir1 constitutively localizes at ER-PM junctions. Nir1 potentiates Nir2 targeting to ER-PM junctions during receptor-mediated signaling and is required for efficient PM PIP2 replenishment. Live-cell imaging and biochemical analysis reveal that Nir1 interacts with Nir2 via a region between the FFAT motif and the DDHD domain. Combined, results from this study identify Nir1 as an ER-PM junction localized protein that promotes Nir2 recruitment for PIP2 homeostasis.
AB - Homeostatic regulation of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2) in receptor-stimulated cells is mediated by the lipid transfer protein Nir2. Nir2 is dynamically recruited to endoplasmic reticulum-plasma membrane (ER-PM) junctions to facilitate replenishment of PM PIP2 hydrolyzed during receptor-mediated signaling. However, our knowledge regarding the activation and sustainment of Nir2-mediated replenishment of PM PIP2 is limited. Here, we describe the functions of Nir1 as a positive regulator of Nir2 and PIP2 homeostasis. In contrast to the family proteins Nir2 and Nir3, Nir1 constitutively localizes at ER-PM junctions. Nir1 potentiates Nir2 targeting to ER-PM junctions during receptor-mediated signaling and is required for efficient PM PIP2 replenishment. Live-cell imaging and biochemical analysis reveal that Nir1 interacts with Nir2 via a region between the FFAT motif and the DDHD domain. Combined, results from this study identify Nir1 as an ER-PM junction localized protein that promotes Nir2 recruitment for PIP2 homeostasis.
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U2 - 10.1091/mbc.E21-07-0356
DO - 10.1091/mbc.E21-07-0356
M3 - Article
C2 - 35020418
AN - SCOPUS:85125000000
SN - 1059-1524
VL - 33
SP - br2
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 3
ER -