{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:51:12Z","timestamp":1785372672423,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"Wellcome Trust","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"Wellcome Trust","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["GR074359"],"award-info":[{"award-number":["GR074359"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["28\/B14085"],"award-info":[{"award-number":["28\/B14085"]}]},{"name":"Biotechnology and Biological Science Research Council","award":["BB\/D523078\/1"],"award-info":[{"award-number":["BB\/D523078\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>\u03b1-Latrotoxin stimulates neurotransmitter release by binding to a presynaptic receptor and then forming ion-permeable membrane pores and\/or stimulating the receptor, latrophilin-1, or Adhesion G-protein-coupled receptor type L1 (ADGRL1). To avoid pore formation, we use the mutant \u03b1-latrotoxin (LTXN4C), which does not form pores and only acts through ADGRL1. ADGRL1 is cleaved into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which behave as independent cell-surface proteins, reassociating upon binding LTXN4C. We investigated the role of the NTF-CTF association in LTXN4C action, using perfluorooctanoic acid (PFOA). We demonstrate that at low concentrations (\u2264100 \u03bcM) PFOA does not adversely affect ADGRL1-expressing neuroblastoma cells or inhibit LTXN4C binding. However, it causes the dissociation of the NTF-CTF complexes, independent redistribution of the fragments on the cell surface, and their separate internalization. PFOA also promotes the dissociation of NTF-CTF complexes induced by LTXN4C binding. When applied to mouse neuromuscular junctions, PFOA inhibits LTXN4C-induced neurotransmitter release in a concentration-dependent manner. Our results indicate that ADGRL1 can mediate LTXN4C signaling only while its fragments remain associated. These findings explain some aspects of receptor-dependent toxin action and contribute to a mechanistic understanding of ADGRL1 functions in neurons.<\/jats:p>","DOI":"10.3390\/toxins17070359","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:47:14Z","timestamp":1753087634000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Dissociation of Latrophilin Fragments by Perfluorooctanoic Acid (PFOA) Inhibits LTXN4C-Induced Neurotransmitter Release"],"prefix":"10.3390","volume":"17","author":[{"given":"Evelina","family":"Petitto","sequence":"first","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-6716","authenticated-orcid":false,"given":"Jennifer K.","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Atiqur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-8297","authenticated-orcid":false,"given":"Yuri A.","family":"Ushkaryov","sequence":"additional","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK"},{"name":"Department of Life Sciences, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/225701a0","article-title":"Effects of Black Widow Spider Venom on the Frog Neuromuscular Junction","volume":"225","author":"Longenecker","year":"1970","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1471-4159.2009.06329.x","article-title":"Penelope\u2019s Web: Using \u03b1-Latrotoxin to Untangle the Mysteries of Exocytosis","volume":"111","author":"Silva","year":"2009","journal-title":"J. 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