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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Kv1.3 is the main voltage-gated potassium channel in T cells. At the immunological synapse (IS), it sustains Ca2\u207a signaling and facilitates T cell activation. Aberrant Kv1.3 expression or activity is linked to autoimmune disorders, yet the mechanisms regulating its targeting and organization at the IS remain unclear. We show that Kv1.3 palmitoylation is a dynamic process mediating channel rearrangement at the IS. The ZDHHC21 acyltransferase, which also S-acylates the TCR, palmitoylates Kv1.3, positioning this enzyme as a potential therapeutic target. Palmitoylation promotes channel migration to the synapse center for removal from the surface. A nonpalmitoylated mutant (Cys\n                    <jats:sub>\n                      <jats:italic>less<\/jats:italic>\n                    <\/jats:sub>\n                    Kv1.3) accumulated at the distal IS and was excluded from lipid raft\u2013enriched domains. Mislocalization and reduced current hindered lymphocyte activation. Moreover, Cys\n                    <jats:sub>\n                      <jats:italic>less<\/jats:italic>\n                    <\/jats:sub>\n                    Kv1.3 showed stronger interaction with PSD95 and cortactin, stabilizing the channel at the surface. These findings highlight S-palmitoylation as a crucial regulator of Kv1.3 during immune responses and a promising target in autoimmune disease therapy.\n                  <\/jats:p>","DOI":"10.1007\/s00018-026-06202-4","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:24:59Z","timestamp":1776493499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kv1.3 palmitoylation regulates spatial distribution and channel removal from the immunological synapse"],"prefix":"10.1007","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8106-9787","authenticated-orcid":false,"given":"Mar\u00eda","family":"Navarro-P\u00e9rez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-8062","authenticated-orcid":false,"given":"Mireia","family":"P\u00e9rez-Verdaguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8049-4806","authenticated-orcid":false,"given":"Anna","family":"Benavente-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4983-6389","authenticated-orcid":false,"given":"Michael L.","family":"Dustin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-6431","authenticated-orcid":false,"given":"Antonio","family":"Felipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-7725","authenticated-orcid":false,"given":"Jesusa","family":"Capera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"6202_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","volume":"33","author":"S Feske","year":"2015","unstructured":"Feske S, Wulff H, Skolnik EY (2015) Ion channels in innate and adaptive immunity. 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