Evidence map›Paper›PMID 25561468›Full record

ArticleMolecular and cellular biology2015

Stability of proICA512/IA-2 and its targeting to insulin secretory granules require β4-sheet-mediated dimerization of its ectodomain in the endoplasmic reticulum.

Juha M Torkko, M Evangelina Primo, Ronald Dirkx, Anne Friedrich, Antje Viehrig, Elisa Vergari, Barbara Borgonovo, Anke Sönmez, Carolin Wegbrod, Martina Lachnit and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. PTPRN promotes glioma cell proliferation, migration, and invasion by regulating the EMT pathway.International journal of clinical and experimental pathology · 2025
    Article
  3. Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family.Medical science monitor : international medical journal of experimental and clinical research · 2024
    Article
  4. Article
  5. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 2 countries.

Juha M TorkkoPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
M Evangelina PrimoUniversity of Buenos Aires, Buenos Aires, Argentina Instituto Multidisciplinario de Biología Celular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Ronald DirkxPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Anne FriedrichPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Antje ViehrigPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Elisa VergariPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Barbara BorgonovoPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Anke SönmezPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Carolin WegbrodPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Martina LachnitPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Carla MünsterPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Mauricio P SicaInstituto Multidisciplinario de Biología Celular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.
Mario R ErmácoraInstituto Multidisciplinario de Biología Celular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.
Michele SolimenaPaul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus, TU Dresden, Germany German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany michele.solimena@tu-dresden.de.
Technische Universität Dresden · DEDeutsches Diabetes-Zentrum e.V. · DEPaul Langerhans Institute Dresden · DEConsejo Nacional de Investigaciones Científicas y Técnicas · ARHeinrich Heine University Düsseldorf · DEInstituto Multidisciplinario de Biología Celular · ARNational University of Quilmes · AR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Amino Acid SequenceAnimalsCells, CulturedCytoplasmic GranulesCytosolDimerizationEndoplasmic ReticulumGlycosylationInsulinIslets of LangerhansMolecular Sequence DataProtein Structure, TertiaryRatsReceptor-Like Protein Tyrosine Phosphatases, Class 8Secretory VesiclesInsulinPtprn protein, ratReceptor-Like Protein Tyrosine Phosphatases, Class 8

Identifiers

PMID25561468
PMCPMC4333099
OpenAlexW2123233568

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.