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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...

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Related Experiment Video

Updated: Jun 13, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Nir1-Nir2 Heterodimerization Confers Robustness to the Phosphoinositide Cycle.

Taylor A Rahn, Wei-Ting Li, Wan-Ru Lee

    Biorxiv : the Preprint Server for Biology
    |June 12, 2026
    PubMed
    Summary

    Researchers discovered how Nir1 and Nir2 proteins form dimers to regulate the phosphatidylinositol (PI) cycle. This dimerization is crucial for maintaining cellular homeostasis and signaling responses to stimuli.

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    Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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    Published on: March 14, 2021

    A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
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    A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

    Published on: January 24, 2016

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    Last Updated: Jun 13, 2026

    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
    08:07

    Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

    Published on: July 26, 2019

    Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
    08:49

    Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

    Published on: March 14, 2021

    A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
    11:44

    A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

    Published on: January 24, 2016

    Area of Science:

    • Cellular signaling
    • Membrane biology
    • Biochemistry

    Background:

    • The phosphatidylinositol (PI) cycle is vital for cellular homeostasis and signaling.
    • Phosphatidylinositol 4,5-bisphosphate (PIP2) levels at the plasma membrane are tightly regulated by the PI cycle.
    • Recruitment of PI transfer protein Nir2 to ER-PM junctions is essential for PI cycle function.

    Purpose of the Study:

    • To elucidate the mechanism of Nir1-mediated recruitment of Nir2 to ER-PM junctions.
    • To define the structural basis of Nir1-Nir2 interaction and its role in regulating the PI cycle.
    • To understand how this interaction impacts cellular signaling and homeostasis.

    Main Methods:

    • Identification and structural determination of the conserved Nir Dimerization (NirD) domain in Nir1 and Nir2.
    • Site-directed mutagenesis to disrupt NirD domain dimerization.
    • Assessment of Nir2 recruitment, PIP2 replenishment, and cellular responses in stimulated cells.

    Main Results:

    • A conserved Nir Dimerization (NirD) domain was identified in Nir1 and Nir2.
    • Disruption of NirD domain dimerization abolished Nir1-dependent Nir2 recruitment and impaired PIP2 replenishment.
    • Nir1-Nir2 dimerization allows graded recruitment of Nir2, enhancing sensitivity and dynamic range of PI cycle responses.

    Conclusions:

    • The NirD domain mediates Nir1-Nir2 dimerization, which is essential for Nir2 recruitment and PI cycle regulation.
    • This dimerization mechanism provides robustness to the PI cycle, enabling precise homeostatic signaling across varying stimulus intensities.
    • The findings reveal a structural basis for regulated protein recruitment in maintaining cellular signaling fidelity.