{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:16:10Z","timestamp":1785413770102,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2023-1481023OB-I00"],"award-info":[{"award-number":["PID2023-1481023OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PID2023-1481023OB-I00"],"award-info":[{"award-number":["PID2023-1481023OB-I00"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red","award":["CIBERER ACCI2023-03-742"],"award-info":[{"award-number":["CIBERER ACCI2023-03-742"]}]},{"award":["CIBERER ACCI2023-03-742"],"award-info":[{"award-number":["CIBERER ACCI2023-03-742"]}],"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Programa Prometeo Generalitat Valenciana","award":["CIPROM2022\/42"],"award-info":[{"award-number":["CIPROM2022\/42"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lafora disease (LD) is a fatal neurodegenerative disorder caused by mutations in the EPM2A or EPM2B\/NHLRC1 genes, encoding Laforin and Malin, respectively. While the Laforin\/Malin E3-ubiquitin ligase complex is a known regulator of canonical autophagy and glycogen metabolism, its role in non-canonical autophagy pathways remains unexplored. Given that neuroinflammation is a hallmark of LD, we investigated the relationship between the Laforin\/Malin complex and Rubicon, a critical regulator of LC3-associated phagocytosis (LAP) and LC3-associated endocytosis (LANDO). In this work, we identify Rubicon as a novel substrate and binding partner of the Laforin\/Malin complex. Co-immunoprecipitation and confocal microscopy assays in HEK293 and U2OS cells demonstrated that Malin physically interacts with Rubicon, promoting its K63-linked polyubiquitination. This post-translational modification adds another layer of control to the regulation of Rubicon in specific cellular contexts. To determine the functional relevance of this interaction in LD, we assessed LAP and LANDO in primary astrocytes from Malin-deficient mice. Using flow cytometry, we quantified the engulfment and degradation of Zymosan particles and microglial debris (LAP), as well as EGF receptor internalization (LANDO). Surprisingly, no significant functional impairments were observed in Malin-deficient astrocytes compared to WT controls. These findings suggest that while the Laforin\/Malin complex regulates Rubicon via K63-linked ubiquitination, redundant signaling nodes may preserve non-canonical autophagy output in Malin-deficient astrocytes.<\/jats:p>","DOI":"10.3390\/ijms27135787","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Role of the Laforin\/Malin Complex in Rubicon-Dependent Phagocytosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Laura","family":"Ba\u00f1os-Carri\u00f3n","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cient\u00edficas, Jaime Roig 11, 46010 Valencia, Spain"},{"name":"Department of Biotechnology, Escuela T\u00e9cnica Superior de Ingenier\u00eda Agron\u00f3mica y del Medio Natural, Universitat Polit\u00e9cnica de Val\u00e8ncia, 46022 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-3912","authenticated-orcid":false,"given":"Maria Adelaida","family":"Garc\u00eda-Gimeno","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Escuela T\u00e9cnica Superior de Ingenier\u00eda Agron\u00f3mica y del Medio Natural, Universitat Polit\u00e9cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4103","authenticated-orcid":false,"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cient\u00edficas, Jaime Roig 11, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF01989438","article-title":"\u00dcber das corkommen amyloider k\u00f6rperchen im innern der ganglienzellen; zugliech ein zum studium der amyloiden substanz im nervensystem","volume":"205","author":"Lafora","year":"1911","journal-title":"Virchows Arch. 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