Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons

Attems, Johannes; Quass, Magdalena; Gärtner, Wolfgang; Nabokikh, Anastasiya; Wagner, Ludwig; Steurer, Stefan; Arbes, Stefanie; Lintner, Felix; Jellinger, K. A.

doi:10.1016/j.exger.2006.09.018

Cited by 22 publications

(44 citation statements)

References 48 publications

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“…SCGN has been shown to have a specific expression pattern (Wagner et al 2000, Gartner et al 2001, BirkenkampDemtroder et al 2005, Lai et al 2006, Attems et al 2007. Especially, the islets of Langerhans are known for highest levels of SCGN expression (Cras-Meneur et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…SCGN is a calcium-binding protein with similarities to calmodulin and calbindin-D28K, which is strongly expressed in pancreatic b-cells, other neuroendocrine cells and distinct neurons of the CNS (Wagner et al 2000, Gartner et al 2001, Cras-Meneur et al 2004, Attems et al 2007, Rogstam et al 2007. SCGN was demonstrated to exert effects on secretion control and transcription processes in b-cells.…”

Section: Introductionmentioning

confidence: 99%

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Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin

Maj¹,

Gärtner²,

İlhan³

et al. 2010

Journal of Endocrinology

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Tauopathies have been associated with Alzheimer's disease (AD), which frequently manifests together with diabetes mellitus type 2. Calcium-binding proteins such as the recently identified secretagogin (SCGN) might exert protective effects. As pancreatic b-cells and neurons share common electrophysiological properties, we investigated the appearance of TAU (listed as MAPT in the HUGO and MGI Databases) protein at the islets of Langerhans and b-cellderived cell lines which highly express the neuroendocrinespecific protein SCGN. Six predominant TAU isoforms could be identified by immunoblotting, which formed TAU deposits detectable by immunofluorescence and sarkosylinsoluble pellets. Using GST-SCGN pull-down assays, a calcium-dependent SCGN-TAU interaction was found. In this line, sucrose density gradient fractionation and differential ultracentrifugation studies of TAU and SCGN revealed co-appearance of both proteins. Co-localization of TAU and SCGN within insulinoma cells and islets of Langerhans mainly restricted to insulin-positive b-cells was demonstrated by confocal microscopy. Motivated by these findings, we looked if SCGN overexpression could exert protective function on Rin-5F cells, which showed differences in TAU levels. Testing the vulnerability of Rin-5F clones by MTT assay, we revealed that high TAU levels going along with highest TAU aggregates could not be antagonized by high levels of SCGN protein. Our findings demonstrated for the first time the association of TAU and the calcium-binding protein SCGN and support earlier results implicating that b-cells might represent an extra cerebral site of tauopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin

Maj¹,

Gärtner²,

İlhan³

et al. 2010

Journal of Endocrinology

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“…The answer is clearly “yes” since secretagogin has recently been demonstrated to identify developmentally-related neuronal subpopulations in the mammalian brain [51,52], including humans [53,54]. Secretagogin is a hexa EF-hand CBP capable to simultaneously bind four Ca 2+ ions [55,56].…”

Section: Introduction: Brief Overview Of Ca2+-binding Proteins Witmentioning

confidence: 99%

The renaissance of Ca2+-binding proteins in the nervous system: secretagogin takes center stage

Alpár

Attems

Mulder

et al. 2012

Cellular Signalling

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Effective control of the Ca2+ homeostasis in any living cell is paramount to coordinate some of the most essential physiological processes, including cell division, morphological differentiation, and intercellular communication. Therefore, effective homeostatic mechanisms have evolved to maintain the intracellular Ca2+ concentration at physiologically adequate levels, as well as to regulate the spatial and temporal dynamics of Ca2+ signalling at subcellular resolution. Members of the superfamily of EF-hand Ca2+-binding proteins are effective to either attenuate intracellular Ca2+ transients as stochiometric buffers or function as Ca2+ sensors whose conformational change upon Ca2+ binding triggers protein-protein interactions, leading to cell state-specific intracellular signalling events. In the central nervous system, some EF-hand Ca2+-binding proteins are restricted to specific subtypes of neurons or glia, with their expression under developmental and/or metabolic control. Therefore, Ca2+-binding proteins are widely used as molecular markers of cell identity whilst also predicting excitability and neurotransmitter release profiles in response to electrical stimuli. Secretagogin is a novel member of the group of EF-hand Ca2+-binding proteins whose expression precedes that of many other Ca2+-binding proteins in postmitotic, migratory neurons in the embryonic nervous system. Secretagogin expression persists during neurogenesis in the adult brain, yet becomes confined to regionalized subsets of differentiated neurons in the adult central and peripheral nervous and neuroendocrine systems. Secretagogin may be implicated in the control of neuronal turnover and differentiation, particularly since it is re-expressed in neoplastic brain and endocrine tumours and modulate cell proliferation in vitro. Alternatively, and since secretagogin can bind to SNARE proteins, it might function as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Thus, secretagogin emerges as a functionally multifaceted Ca2+-binding protein, whose molecular characterization can unravel a new and fundamental dimension of Ca2+ signalling under physiological and disease conditions in the nervous system and beyond.

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“…Secretagogin belongs to the EF-hand family Ca 2ϩ -binding proteins, which exert their Ca 2ϩ -binding capacity via the evolutionary highly conserved helix-loop-helix EF-hand motifs (9,18,23,31). In addition to its strong expression in ␤-cells, secretagogin is also found in other endocrine tissues and in distinct neurons of the central nervous system (4,8,16,37). Although the exact function of secretagogin is still a matter of research, its strong expression in insulin-secreting cells (10,48), its influence on insulin expression (46), and recent data indicating glucoseinduced upregulation of secretagogin expression in ␤-cells (1,43) highlight the functional importance of this Ca 2ϩ -binding protein in pancreatic ␤-cells.…”

mentioning

confidence: 99%

New functional aspects of the neuroendocrine marker secretagogin based on the characterization of its rat homolog

Gärtner

Vila²,

Daneva³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Secretagogin is a recently cloned human beta-cell-expressed EF-hand Ca(2+)-binding protein. Converging evidence indicates that it exerts Ca(2+) sensor activity and is involved in regulation of insulin synthesis and secretion. To obtain a potent tool for the extension of its functional analysis in rat in vitro systems, we cloned the rat homolog of human secretagogin. Using comparative sequence analysis, immunostaining, and immunoblotting, we demonstrated a high degree of sequence homology and similar tissue expression patterns of human and rat secretagogin. Highest rat secretagogin expression levels were found in pancreatic beta-cells. On the basis of newly generated anti-rat secretagogin antibodies, we established a rat secretagogin-specific sandwich capture ELISA and demonstrated release of secretagogin from viable Rin-5F cells. Dexamethasone treatment of Rin-5F cells resulted in an increased secretagogin release rate, which was inversely correlated with insulin secretion. In contrast, the secretagogin transcription rate was markedly reduced. This resulted in a decreased intracellular secretagogin content under the influence of dexamethasone. Sucrose gradient cell fractionation analysis of Rin-5F cells confirmed the predominant cytosolic localization of secretagogin, with only limited association of secretagogin with insulin granules. The loss of intracellular secretagogin after dexamethasone treatment affected predominantly the insulin granule-associated secretagogin fractions. The sequence homology and the comparable tissue expression patterns of human and rat secretagogin indicate conserved intracellular functions. The effects of dexamethasone on the total secretagogin content in Rin-5F cells and on its intracellular distribution might result in an impaired Ca(2+) sensitivity of dexamethasone-treated insulin-secreting cells.

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Immunoreactivity of calcium binding protein secretagogin in the human hippocampus is restricted to pyramidal neurons

Cited by 22 publications

References 48 publications

Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin

Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin

The renaissance of Ca2+-binding proteins in the nervous system: secretagogin takes center stage

New functional aspects of the neuroendocrine marker secretagogin based on the characterization of its rat homolog

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