{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:51:49Z","timestamp":1785372709571,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The elimination of transformed and viral infected cells by natural killer (NK) cells requires a specialized junction between NK and target cells, denominated immunological synapse (IS). After initial recognition, the IS enables the directed secretion of lytic granules content into the susceptible target cell. The lymphocyte function\u2010associated antigen (LFA)\u20101 regulates NK effector function by enabling NK\u2010IS assembly and maturation. The pathways underlying LFA\u20101 accumulation at the IS in NK cells remained uncharacterized. A kinase anchoring protein 350 (AKAP350) is a centrosome\/Golgi\u2010associated protein, which, in T cells, participates in LFA\u20101 activation by mechanisms that have not been elucidated. We first evaluated AKAP350 participation in NK cytolytic activity. Our results showed that the decrease in AKAP350 levels by RNA interference (AKAP350KD) inhibited NK\u2010YTS cytolytic activity, without affecting conjugate formation. The impairment of NK effector function in AKAP350KD cells correlated with decreased LFA\u20101 clustering and defective IS maturation. AKAP350KD cells that were exclusively activated via LFA\u20101 showed impaired LFA\u20101 organization and deficient lytic granule translocation as well. In NK AKAP350KD cells, activation signaling through Vav1 was preserved up to 10\u2009min of interaction with target cells, but significantly decreased afterwards. Experiments in YTS and in ex vivo NK cells identified an intracellular pool of LFA\u20101, which partially associated with the Golgi apparatus and, upon NK activation, redistributed to the IS in an AKAP350\u2010dependent manner. The analysis of Golgi organization indicated that the decrease in AKAP350 expression led to the disruption of the Golgi integrity in NK cells. Alteration of Golgi function by BFA treatment or AKAP350 delocalization from this organelle also led to impaired LFA\u20101 localization at the IS. Therefore, this study characterizes AKAP350 participation in the modulation of NK effector function, revealing the existence of a Golgi\u2010dependent trafficking pathway for LFA\u20101, which is relevant for LFA\u20101 organization at NK\u2010lytic IS.<\/jats:p>","DOI":"10.1002\/jcp.30921","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T14:05:37Z","timestamp":1670421937000},"page":"227-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of a novel mechanism for LFA\u20101 organization during NK cytolytic response"],"prefix":"10.1002","volume":"238","author":[{"given":"Alejandro P.","family":"Pariani","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario (UNR) Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelina","family":"Almada","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda Cl\u00ednica y Experimental de Rosario CONICET\u2010UNR Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario (UNR) Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Borini\u2010Etichetti","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario (UNR) Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Vena","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario CONICET\u2010UNR Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario (UNR) Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristi\u00e1n","family":"Favre","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas Universidad Nacional de Rosario (UNR) Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Goldenring","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center and Department of Cell &amp; 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