Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion

Bauer, Mikael C.; O’Connell, David J.; Maj, Magdalena; Wagner, Ludwig; Cahill, Dolores J.; Linse, Sara

doi:10.1039/c0mb00349b

Cited by 36 publications

(39 citation statements)

References 42 publications

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“…Secretagogin is a Ca 2+ sensing protein that changes its conformation when [Ca 2+ ] i rises, allowing its interaction with exocytotic proteins like SNAP25 and Doc2alpha 29 . Accordingly, we observed that secretagogin interacts with tomosyn under basal conditions, and this is decreased in response to glucose and KCl, the latter finding suggesting an important role for [Ca 2+ ] i as opposed to glucose-dependent metabolic signals.…”

Section: Discussionmentioning

confidence: 99%

SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

Ferdaoussi

Dai

et al. 2017

Sci Rep

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Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2+. Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca2+-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca2+ influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca2+ to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.

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Section: Discussionmentioning

confidence: 99%

SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

Ferdaoussi

Dai

et al. 2017

Sci Rep

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“…Its tertiary structure changes upon Ca 2+ -binding [55]. This property, together with an in vitro -identified cellular interaction network [57], suggests that secretagogin may act as a Ca 2+ sensor rather than buffer in neurons. This review summarizes experimental and histopathological data hitherto obtained and concerned with secretagogin's structure, expression pattern, physiological and pathological significance and discusses critical experiments to conclusively define secretagogin functions in the central nervous system (CNS).…”

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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“…Here, we show that the supraoptic nucleus (nucleus decussationis supraopticae, pars ventralis) is densely packed with secretagogin + neurons with further cell groups present in the lateral hypothalamus, and paraventricular and infundibular nuclei. Since secretagogin was shown to impact vesicle secretion and release Bauer et al, 2011;Hasegawa et al, 2013], it is conceivable that secretagogin plays a role in the control of hypothalamic hormone secretion/release.…”

Section: + -Binding Proteinsmentioning

confidence: 99%

“…Given its relatively low Ca 2+ -binding affinity and conformational modifications upon Ca 2+ binding, secretagogin qualifies as a Ca 2+ sensor [Rogstam et al, 2007]. The predicted interactome of secretagogin includes members of SNARE (soluble NSF attachment protein receptor) superfamily of proteins, suggesting its involvement in regulating secretory and synaptic vesicle trafficking and activity-dependent release [Rogstam et al, 2007;Bauer et al, 2011;Hasegawa et al, 2013]. Secretagogin is expressed in essentially all organ systems [Wagner et al, 2000;Alpár et al, 2012].…”

Section: Introductionmentioning

confidence: 99%

Revival of Calcium-Binding Proteins for Neuromorphology: Secretagogin Typifies Distinct Cell Populations in the Avian Brain

Gáti

Lendvai

Hökfelt³

et al. 2014

Brain Behav Evol

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In the vertebrate nervous system, the Ca²⁺-binding proteins parvalbumin, calbindin and calretinin have been extensively used to elaborate the molecular diversity of neuronal subtypes. Secretagogin is a phylogenetically conserved Ca²⁺-binding protein, which marks neuronal populations largely distinct from other Ca²⁺-binding proteins in mammals. Whether secretagogin is expressed in nonmammalian vertebrates, particularly in birds, and, if so, with a brain cytoarchitectonic design different from that of mammals is unknown. Here, we show that secretagogin is already present in the hatchlings' brain with continued presence into adulthood. Secretagogin-immunoreactive neurons primarily accumulate in the olfactory bulb, septum, subpallial amygdala, hippocampus, hypothalamus, habenular nuclei and deep layers of the optic tectum of adult domestic chicks (Gallus domesticus). In the olfactory bulb, secretagogin labels periglomerular neurons as well as a cell continuum ascending dorsomedially, reaching the ventricular wall. Between the hippocampus and septal nuclei, the interconnecting thin septal tissue harbors secretagogin-immunoreactive neurons that contact the ventricular wall with their ramifying dendritic processes. Secretagogin is also present in the neuroendocrine hypothalamus, with particularly rich neuronal clusters seen in its suprachiasmatic and infundibular nuclei. Secretagogin expression identified a hitherto undescribed cell contingent along intratelencephalic cell-free laminae separating brain regions or marking the palliosubpallial boundary, as well as a dense neuronal population in the area corticoidea lateralis. In both the telencephalon and midbrain, secretagogin complemented the distribution of the canonical ‘neuronal' Ca²⁺-binding proteins. Our findings identify novel neuronal subtypes, connectivity patterns in brain areas functionally relevant to olfaction, orientation, behavior as well as endocrine functions, which will help refine existing concepts on the neuronal diversity and organizational principles of the avian brain.

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Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion

Cited by 36 publications

References 42 publications

SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells

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

Revival of Calcium-Binding Proteins for Neuromorphology: Secretagogin Typifies Distinct Cell Populations in the Avian Brain

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