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Campo DC | Valor | Lengua/Idioma |
---|---|---|
dc.provenance | Comisión de Investigaciones Científicas | - |
dc.contributor | Torkko, J. | - |
dc.contributor | Primo, M. | - |
dc.contributor | Dirkx, R. | - |
dc.contributor | Friedrich, A. | - |
dc.contributor | Viehrig, A. | - |
dc.contributor | Vergari, E. | - |
dc.contributor | Borgonovo, B. | - |
dc.contributor | Sonmez, A. | - |
dc.contributor | Wegbrod, C. | - |
dc.contributor | Lachnit, M. | - |
dc.contributor | Munster, C. | - |
dc.contributor | Sica, Mauricio | - |
dc.contributor | Emárcora, M. | - |
dc.contributor | Solimena, M. | - |
dc.creator | Torkko, J. | - |
dc.creator | Primo, M. | - |
dc.creator | Dirkx, R. | - |
dc.creator | Friedrich, A. | - |
dc.creator | Viehrig, A. | - |
dc.creator | Vergari, E. | - |
dc.creator | Borgonovo, B. | - |
dc.creator | Sonmez, A. | - |
dc.creator | Wegbrod, C. | - |
dc.creator | Lachnit, M. | - |
dc.creator | Munster, C. | - |
dc.creator | Sica, Mauricio | - |
dc.creator | Emárcora, M. | - |
dc.creator | Solimena, M. | - |
dc.date | 2015 | - |
dc.date.accessioned | 2019-04-29T16:11:36Z | - |
dc.date.available | 2019-04-29T16:11:36Z | - |
dc.date.issued | 2015 | - |
dc.identifier | http://digital.cic.gba.gob.ar/handle/11746/4227 | - |
dc.identifier | Recurso Completo | - |
dc.identifier.uri | http://rodna.bn.gov.ar:8080/jspui/handle/bnmm/311362 | - |
dc.description | The 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.format | application/pdf | - |
dc.format | 49 p. | - |
dc.language | eng | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.rights | Attribution 4.0 International (BY 4.0) | - |
dc.source | reponame:CIC Digital (CICBA) | - |
dc.source | instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Aires | - |
dc.source | instacron:CICBA | - |
dc.source.uri | http://digital.cic.gba.gob.ar/handle/11746/4227 | - |
dc.source.uri | Recurso Completo | - |
dc.subject | Biología Celular, Microbiología | - |
dc.title | Stability and targeting of proICA512/IA-2 to insulin secretory granules requires beta4-sheet mediated dimerization of its ectodomain in the endoplasmic reticulum | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.type | info:ar-repo/semantics/articulo | - |
Aparece en las colecciones: | Comisión de Investigaciones Científicas de la Prov. de Buenos Aires |
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