ArticleDevelopmental cell2018
The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.
Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- T-betThe FEBS journal · 2026Article
- TCRζ-driven pre-signaling organization of Lck in Rab11⁺ endosomes shapes TCR activation.Cellular & molecular biology letters · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Pathogenic CD8+ T cells target K71+ Henle's layer by forming cytolytic immune synapses in Alopecia Areata.Research square · 2026Article
- Spatial regulation of Lck activation at the CD8 immune synapse revealed by a FRET-Based biosensor.Cellular and molecular life sciences : CMLS · 2026Article
- Combining antigen specific T-cells with T-cell engager therapy induces a molecular signature that favors T-cell fitness.Blood immunology & cellular therapy · 2025Article
- UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.Life science alliance · 2025Article
- BMP-ACVR1 Axis is Critical for Efficacy of PRC2 Inhibitors in B-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.Communications biology · 2023Article
- Patterns of Ciliation and Ciliary Signaling in Cancer.Reviews of physiology, biochemistry and pharmacology · 2023Review
- Multiplexed high-throughput immune cell imaging reveals molecular health-associated phenotypes.Science advances · 2022Article
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- The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly.Journal of cell science · 2021Article
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- The Structural and Biochemical Characterization of UNC119B Cargo Binding and Release Mechanisms.Biochemistry · 2021Article
- Teasing out function from morphology: Similarities between primary cilia and immune synapses.The Journal of cell biology · 2021Review
- ARL3, a small GTPase with a functionally conserved role in primary cilia and immune synapses.Small GTPases · 2021Review
- Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance.EMBO reports · 2021Article
- Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections.iScience · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a "regulatory arm" by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse.
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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.