ArticleThe Journal of experimental medicine2013
The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Pooled it
- LSD1 Promotes Immune Exclusion and Suppresses IFN-γ-Associated Transcriptional Programs in Triple-Negative Breast Cancer.Cancers · 2026Article
- Review
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Macrophage migration inhibitory factor: Exploring physiological roles and comparing health benefits against oncogenic and autoimmune risks (Review).International journal of molecular medicine · 2025Review
- Integrated analysis of COVID-19 multi-omics data for eQTLs reveals genetic mechanisms underlying disease severity.bioRxiv : the preprint server for biology · 2025Article
- The N-terminal PA domains of signal-peptide-peptidase-like 2 (SPPL2) proteases impact on TNFα cleavage.Communications biology · 2025Article
- Distinctive Macrophage Migration Inhibitory Factor Receptor Patterns and Soluble Biomarkers in Rheumatoid Arthritis: Unveiling Key Associations with Disease Activity.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Selective regulation of aspartyl intramembrane protease activity by calnexin.Cellular and molecular life sciences : CMLS · 2024Article
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- CD74 is a functional MIF receptor on activated CD4Cellular and molecular life sciences : CMLS · 2024Article
- Genome-Wide Identification of the SPP/SPPL Gene Family andInternational journal of molecular sciences · 2024Article
- Genome-wide detection of human intronic AG-gain variants located between splicing branchpoints and canonical splice acceptor sites.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dynamic association of the intramembrane proteases SPPL2a/b and their substrates with tetraspanin-enriched microdomains.iScience · 2023Article
- The transmembrane domain of Frey1 harbors a transplantable inhibitory motif for intramembrane proteases.Cellular and molecular life sciences : CMLS · 2023Article
- Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical, Immunological, and Genetic Features of 22 Patients from 15 Moroccan Kindreds.Journal of clinical immunology · 2023Article
- Article
- Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.Nature communications · 2022Article
- Lysosomes and lysosome-related organelles in immune responses.FEBS open bio · 2022Review
- The transmembrane domain and luminal C-terminal region independently support invariant chain trimerization and assembly with MHCII into nonamers.BMC immunology · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells.
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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.