1. RODNA
  2. CIC Digital
  3. Comisión de Investigaciones Científicas de la Prov. de Buenos Aires
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dc.provenanceComisión de Investigaciones Científicas-
dc.contributorTorkko, Juha M.-
dc.contributorPrimo, María Evangelina-
dc.contributorDirkx, Ronald-
dc.contributorFriedrich, Anne-
dc.contributorViehrig, Antje-
dc.contributorVergari, Elisa-
dc.contributorBorgonovo, Bárbara-
dc.contributorSönmez, Anke-
dc.contributorWegbrod, Carolin-
dc.contributorLachnit, Martina-
dc.contributorMünster, Carla-
dc.contributorSica, Mauricio-
dc.contributorErmácora, Mario-
dc.contributorSolimena, Michele-
dc.creatorTorkko, Juha M.-
dc.creatorPrimo, María Evangelina-
dc.creatorDirkx, Ronald-
dc.creatorFriedrich, Anne-
dc.creatorViehrig, Antje-
dc.creatorVergari, Elisa-
dc.creatorBorgonovo, Bárbara-
dc.creatorSönmez, Anke-
dc.creatorWegbrod, Carolin-
dc.creatorLachnit, Martina-
dc.creatorMünster, Carla-
dc.creatorSica, Mauricio-
dc.creatorErmácora, Mario-
dc.creatorSolimena, Michele-
dc.date2015-03-
dc.date.accessioned2019-04-29T16:03:56Z-
dc.date.available2019-04-29T16:03:56Z-
dc.date.issued2015-03-
dc.identifierhttp://digital.cic.gba.gob.ar/handle/11746/2283-
dc.identifierDocumento completo-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/308261-
dc.descriptionThe type 1 diabetes autoantigen ICA512/IA-2/RPTPN is a receptor protein tyrosine phosphatase of the insulin secretory granules (SGs) which regulates the size of granule stores, possibly via cleavage/signaling of its cytosolic tail. The role of its extracellular region remains unknown. Structural studies indicated that β2- or β4-strands in the mature ectodomain (ME ICA512) form dimers in vitro. Here we show that ME ICA512 prompts proICA512 dimerization in the endoplasmic reticulum. Perturbation of ME ICA512 β2-strand N-glycosylation upon S508A replacement allows for proICA512 dimerization, O-glycosylation, targeting to granules, and conversion, which are instead precluded upon G553D replacement in the ME ICA512 β4-strand. S508A/G553D and N506A/G553D double mutants dimerize but remain in the endoplasmic reticulum. Removal of the N-terminal fragment (ICA512-NTF) preceding ME ICA512 allows an ICA512-ΔNTF G553D mutant to exit the endoplasmic reticulum, and ICA512-ΔNTF is constitutively delivered to the cell surface. The signal for SG sorting is located within the NTF RESP18 homology domain (RESP18-HD), whereas soluble NTF is retained in the endoplasmic reticulum. Hence, we propose that the ME ICA512 β2-strand fosters proICA512 dimerization until NTF prevents N506 glycosylation. Removal of this constraint allows for proICA512 β4-strand-induced dimerization, exit from the endoplasmic reticulum, O-glycosylation, and RESP18-HD-mediated targeting to granules.-
dc.formatapplication/pdf-
dc.formatp. 914-927-
dc.languageeng-
dc.publisherAmerican Society for Microbiology-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightsAttribution 4.0 International (BY 4.0)-
dc.sourcereponame:CIC Digital (CICBA)-
dc.sourceinstname:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires-
dc.sourceinstacron:CICBA-
dc.source.urihttp://digital.cic.gba.gob.ar/handle/11746/2283-
dc.source.uriDocumento completo-
dc.subjectBiología Celular, Microbiología-
dc.titleStability and targeting of proICA512/IA-2 to insulin secretory granules requires β4-sheet mediated dimerization of its ectodomain in the endoplasmic reticulum-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/acceptedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
Aparece en las colecciones: Comisión de Investigaciones Científicas de la Prov. de Buenos Aires

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