Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen.

Pietropaolo, Massimo; Castaño, Luís; Babu, Sunanda; Buelow, Roland; Kuo, Yu-Min; Martin, Stéphan; Martin, Anne F.; Powers, Alvin C.; Procházka, Michal; Naggert, Jürgen Κ.

doi:10.1172/jci116574

Cited by 224 publications

(130 citation statements)

References 73 publications

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“…Materials-The following antibodies were used: affinity-purified rabbit antibodies against residues 471-483 of human ICA69 (pICA69) (1) and against ICA512 ectodomain (9); mouse monoclonal antibodies against human ICA69 (mICA69); GAD65 (9); ␤ЈCOP (Drs. J. Fuellekrug and K. Simons, Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany); the 18-kDa fragment of secretogranin II (Dr. S. Tooze, Cancer UK, London, UK) (10, 11); giantin (Dr. H.-P. Hauri, Biozentrum, Basel, Switzerland) (12); TGN38, GM130, syntaxin 6, and carboxypeptidase E/H (BD Transduction Laboratories, Heidelberg, Germany); ARF1 (Affinity Bioreagents, Golden, CO); proinsulin (nonreactive against insulin) (Research Diagnostics); synaptophysin (Synaptic Systems, Goettingen, Germany); transferrin receptor (Zymed Laboratories, South San Francisco, CA); insulin and ␥-tubulin (Sigma), goat anti-rabbit and anti-mouse IgGs conjugated to Alexa 488 or Alexa 568 (Molecular Probes, Inc., Eugene, OR); and goat anti-rabbit and goat anti-mouse IgGs conjugated with gold particles (Electron Microscopy Sciences, Fort Washington, PA).…”

Section: Methodsmentioning

confidence: 99%

“…: 49-351-458-6611; Fax: 49-351-458-6330; E-mail: michele.solimena@mailbox.tudresden.de. 1 The abbreviations used are: ICA69, islet cell autoantigen of 69 kDa; BFA, brefeldin A; CPE, carboxypeptidase E; GAD65, glutamic acid decarboxylase of 65 kDa; ISG, immature secretory granule; MTOC, microtubule organizing center; PNS, postnuclear supernatant; MSGs, mature secretory granules; SG, secretory granule; SVs, synaptic vesicles; SLMVs, synaptic-like microvesicles; TGN, trans-Golgi network.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, our findings raise the possibility that ICA69 acts in concert with small GTPases in regulating membrane dynamics at the Golgi complex and ISGs. The wide tissue expression of ICA69 (1,4,5), suggests that this regulation may not be restricted to neuroendocrine cells.…”

Section: Enrichment Of Ica69 On the Golgi Complex By Subcellularmentioning

confidence: 99%

“…Originally identified by immunoscreening of an islet cDNA expression library with prediabetic sera, islet cell autoantigen of 69 kDa (ICA69) 1 is an evolutionary conserved gene with homologues in the nonmammalian model organisms Drosophila melanogaster and Caenorhabditis elegans (1)(2)(3). Like most antigens of type 1 diabetes, ICA69 is enriched in pancreatic ␤-cells and neurons (4).…”

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confidence: 99%

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Islet Cell Autoantigen of 69 kDa Is an Arfaptin-related Protein Associated with the Golgi Complex of Insulinoma INS-1 Cells

Spitzenberger

Pietropaolo

Verkade

et al. 2003

Journal of Biological Chemistry

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Islet cell autoantigen of 69 kDa (ICA69) is a cytosolic protein of still unknown function. Involvement of ICA69 in neurosecretion has been suggested by the impairment of acetylcholine release at neuromuscular junctions upon mutation of its homologue gene ric-19 in C. elegans. In this study, we have further investigated the localization of ICA69 in neurons and insulinoma INS-1 cells. ICA69 was enriched in the perinuclear region, whereas it did not co-localize with markers of synaptic vesicles/synaptic-like microvesicles. Confocal microscopy and subcellular fractionation in INS-1 cells showed co-localization of ICA69 with markers of the Golgi complex and, to a minor extent, with immature insulin-containing secretory granules. The association of ICA69 with these organelles was confirmed by immunoelectron microscopy. Virtually no ICA69 immunogold labeling was observed on secretory granules near the plasma membrane, suggesting that ICA69 dissociates from secretory granule membranes during their maturation. In silico sequence and structural analyses revealed that the N-terminal region of ICA69 is similar to the region of arfaptins that interacts with ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. ICA69 is therefore a novel arfaptin-related protein that is likely to play a role in membrane trafficking at the Golgi complex and immature secretory granules in neurosecretory cells.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Enrichment Of Ica69 On the Golgi Complex By Subcellularmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Islet Cell Autoantigen of 69 kDa Is an Arfaptin-related Protein Associated with the Golgi Complex of Insulinoma INS-1 Cells

Spitzenberger

Pietropaolo

Verkade

et al. 2003

Journal of Biological Chemistry

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show abstract

“…However, very little is known about the role of viruses in the initiation of human IDDM. Progressive autoimmunity in IDDM is characterized by a chronic mononuclear cell infiltration of pancreatic islet cells [6] and the presence of autoantibodies to beta cell antigens, including islet cell autoantibodies (ICA) [7], insulin antibodies [8], antibodies to glutamic acid decarboxylase (GAD) [9], ICA69 [10], and antibodies to tyrosine phosphatase ICA512/IA2 [11]. In addition to activation of humoral immunity, the stimulation of cellular immunity against insulin [12], GAD [13], 38 kDa secretory protein known as mitochondrial imogen 38 [14,15], and hsp65 [16] has been reported.…”

Section: Introductionmentioning

confidence: 99%