ArticleImmunity2018
PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes.
Article in Immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- Actin conformation dynamics precede force generation in cytotoxic T lymphocytes.Communications biology · 2026Article
- CD28-mediated linear and parallel costimulatory signaling cooperatively regulate CAR-T cell functions via CAR-CD28 microclusters.Communications biology · 2025Article
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Reciprocal regulation between AtFH5-labeled secretory vesicles and PI(4,5)PJournal of integrative plant biology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Nonlinear dynamics in phosphoinositide metabolism.Current opinion in cell biology · 2024Review
- Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls cell sensitivity to interferon.Developmental cell · 2024Article
- Extended-Synaptotagmin-1 and -2 control T cell signaling and function.EMBO reports · 2024Article
- Phosphoinositide Signaling in Immune Cell Migration.Biomolecules · 2023Review
- Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.Molecular psychiatry · 2023Article
- INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.Communications biology · 2023Article
- Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse.Science (New York, N.Y.) · 2023Article
- Recent advances in understanding TCR signaling: a synaptic perspective.Faculty reviews · 2023Review
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- A CVID-associated variant in the ciliogenesis protein CCDC28B disrupts immune synapse assembly.Cell death and differentiation · 2022Article
- Cytotoxic T Lymphocyte Activation Signals Modulate Cytoskeletal Dynamics and Mechanical Force Generation.Frontiers in immunology · 2022Article
- The Immunological Synapse: An Emerging Target for Immune Evasion by Bacterial Pathogens.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
How cytotoxic T lymphocytes (CTLs) sense T cell receptor (TCR) signaling in order to specialize an area of plasma membrane for granule secretion is not understood. Here, we demonstrate that immune synapse formation led to rapid localized changes in the phosphoinositide composition of the plasma membrane, both reducing phosphoinositide-4-phosphate (PI(4)P), PI(4,5)P2, and PI(3,4,5)P3 and increasing diacylglycerol (DAG) and PI(3,4)P2 within the first 2 min of synapse formation. These changes reduced negative charge across the synapse, triggering the release of electrostatically bound PIP5 kinases that are required to replenish PI(4,5)P2. As PI(4,5)P2 decreased, actin was depleted from the membrane, allowing secretion. Forced localization of PIP5Kβ across the synapse prevented actin depletion, blocking both centrosome docking and secretion. Thus, PIP5Ks act as molecular sensors of TCR activation, controlling actin recruitment across the synapse, ensuring exquisite co-ordination between TCR signaling and CTL secretion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.