{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:45:18Z","timestamp":1775274318279,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["P01NS097197"],"award-info":[{"award-number":["P01NS097197"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lafora disease (LD) is a fatal rare type of progressive myoclonus epilepsy that appears during early adolescence. The disease is caused by mutations in <jats:italic>EPM2A<\/jats:italic> or <jats:italic>EPM2B<\/jats:italic> genes, which encode laforin, a glucan phosphatase, and malin, an E3\u2010ubiquitin ligase, respectively. Although the exact roles of laforin and malin are still not well understood, it is known that they work as a complex in which laforin recruits targets that will be ubiquitinated by malin. Recently, we suggested that the type of epilepsy that accompanies LD could be due to deficiencies in the function of the astrocytic glutamate transporter GLT\u20101. We described that astrocytes from LD mouse models presented decreased levels of GLT\u20101 at the plasma membrane, leading to increased levels of glutamate in the brain parenchyma. In this work, we present evidence indicating that in the absence of a functional laforin\/malin complex (as in LD cellular models) there is an alteration in the ubiquitination of GLT\u20101, which could be the cause of the reduction in the levels of GLT\u20101 at the plasma membrane. On the contrary, overexpression of the laforin\/malin complex promotes the retention of GLT\u20101 at the plasma membrane. This retention may be due to the direct ubiquitination of GLT\u20101 and\/or to an opposite effect of this complex on the dynamics of the Nedd4.2\u2010mediated endocytosis of the transporter. This work, therefore, presents new pieces of evidence on the regulation of GLT\u20101 by the laforin\/malin complex, highlighting its value as a therapeutic target for the amelioration of the type of epilepsy that accompanies LD.<\/jats:p>","DOI":"10.1002\/glia.23956","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T15:58:38Z","timestamp":1608825518000},"page":"1170-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Endocytosis of the glutamate transporter 1 is regulated by laforin and malin: Implications in <scp>Lafora<\/scp> disease"],"prefix":"10.1002","volume":"69","author":[{"given":"Eva","family":"Perez\u2010Jimenez","sequence":"first","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Viana","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-7753","authenticated-orcid":false,"given":"Carmen","family":"Mu\u00f1oz\u2010Ballester","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Vendrell\u2010Tornero","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Moll\u2010Diaz","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Adelaida","family":"Garcia\u2010Gimeno","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Polythecnic University of Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4103","authenticated-orcid":false,"given":"Pascual","family":"Sanz","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cient\u00edficas Instituto de Biomedicina de Valencia  Valencia Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras Instituto de Biomedicina de Valencia  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23463"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004898"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9091-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03629.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.07.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403938200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1238"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0758-y"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00067-8"},{"issue":"8","key":"e_1_2_8_11_1","first-page":"8","article-title":"Lafora disease: A Ubiquitination\u2010related pathology","volume":"7","author":"Garcia\u2010Gimeno M. 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