{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Medlyn MJ"],"funding":["National Institute of Allergy and Infectious Diseases","Mayo Foundation","NIAID NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["jcs261582"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11058345"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["137(7)"],"pubmed_abstract":["Natural killer (NK) cells have the ability to lyse other cells through the release of lytic granules (LGs). This is in part mediated by the small GTPase Rab27a, which was first identified to play a crucial role in degranulation through the study of individuals harboring mutations in the gene encoding Rab27a. However, the guanine nucleotide exchange factor (GEF) regulating the activation of Rab27a in cytotoxic lymphocytes was unknown. Here, we show that knockout of MADD significantly decreased the levels of GTP-bound Rab27a in both resting and stimulated NK cells, and MADD-deficient NK cells and CD8+ T cells displayed severely reduced degranulation and cytolytic ability, similar to that seen with Rab27a deficiency. Although MADD colocalized with Rab27a on LGs and was enriched at the cytolyt"],"journal":["Journal of cell science"],"pubmed_title":["MADD regulates natural killer cell degranulation through Rab27a activation."],"pmcid":["PMC11058345"],"funding_grant_id":["T32 AI07425-25","R01-AI120949","R01 AI120949","T32 AI007425"],"pubmed_authors":["Maeder E","Ham H","Medlyn MJ","Billadeau DD","Bradley C","Phatarpekar P"],"additional_accession":[]},"is_claimable":false,"name":"MADD regulates natural killer cell degranulation through Rab27a activation.","description":"Natural killer (NK) cells have the ability to lyse other cells through the release of lytic granules (LGs). This is in part mediated by the small GTPase Rab27a, which was first identified to play a crucial role in degranulation through the study of individuals harboring mutations in the gene encoding Rab27a. However, the guanine nucleotide exchange factor (GEF) regulating the activation of Rab27a in cytotoxic lymphocytes was unknown. Here, we show that knockout of MADD significantly decreased the levels of GTP-bound Rab27a in both resting and stimulated NK cells, and MADD-deficient NK cells and CD8+ T cells displayed severely reduced degranulation and cytolytic ability, similar to that seen with Rab27a deficiency. Although MADD colocalized with Rab27a on LGs and was enriched at the cytolyt","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2025-06-26T03:06:06.327Z","creation":"2025-06-26T03:06:06.327Z"},"accession":"S-EPMC11058345","cross_references":{"pubmed":["38506245"],"doi":["10.1242/jcs.261582"]}}