The renaissance of Ca 2+-binding proteins in the nervous system: Secretagogin takes center stage

European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen, United Kingdom.
Cellular Signalling (Impact Factor: 4.32). 02/2012; 24(2):378-87. DOI: 10.1016/j.cellsig.2011.09.028
Source: PubMed


Effective control of the Ca(2+) 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 Ca(2+) concentration at physiologically adequate levels, as well as to regulate the spatial and temporal dynamics of Ca(2+)signaling at subcellular resolution. Members of the superfamily of EF-hand Ca(2+)-binding proteins are effective to either attenuate intracellular Ca(2+) transients as stochiometric buffers or function as Ca(2+) sensors whose conformational change upon Ca(2+) binding triggers protein-protein interactions, leading to cell state-specific intracellular signaling events. In the central nervous system, some EF-hand Ca(2+)-binding proteins are restricted to specific subtypes of neurons or glia, with their expression under developmental and/or metabolic control. Therefore, Ca(2+)-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 Ca(2+)-binding proteins whose expression precedes that of many other Ca(2+)-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 tumors and modulates cell proliferation in vitro. Alternatively, and since secretagogin can bind to SNARE proteins, it might function as a Ca(2+) sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Thus, secretagogin emerges as a functionally multifaceted Ca(2+)-binding protein whose molecular characterization can unravel a new and fundamental dimension of Ca(2+)signaling under physiological and disease conditions in the nervous system and beyond.

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Available from: Jan Mulder, Oct 14, 2015
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    • "Ca2+ ions are crucial second messengers in synaptic transmission and cytoskeleton function. Ca2+ binding proteins of different classes play important roles in the brain [1]. Swiprosin-1/EFhd2 (EFhd2) is a proposed Ca2+ sensor protein expressed abundantly in the brain [2], [3], and was shown to interact with tauP301L [4]. "
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    ABSTRACT: Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.
    PLoS ONE 08/2014; 9(8):e103976. DOI:10.1371/journal.pone.0103976 · 3.23 Impact Factor
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    ABSTRACT: Juxtaglomerular neurons in the mouse main olfactory bulb consist of various types of neurons, especially classified by their chemical properties such as transmitter-related molecules and calcium binding proteins. In addition several transcription factors have been revealed to characterize neuronal subpopulations. In this study we examined the immunoreactivities of two transcription factors, Sp8 and Tbx21, in the juxtaglomerular neuronal subpopulations containing calretinin, calbindin, secretagogin, tyrosine hydroxylase (TH) and nitric oxide synthase (NOS). Both Sp8 and Tbx21 immunoreactivities were so diverse in their staining intensities. Almost all calretinin and secretagogin positive neurons were relatively strongly Sp8 positive, whereas none of calbindin positive neurons were Sp8 positive. TH positive neurons were also usually Sp8 positive, although some were faintly positive. These four types of interneurons were Tbx21 negative. On the other hand large faintly NOS positive external tufted cells were occasionally Tbx21 positive but always Sp8 negative, whereas small NOS positive periglomerular cells without distinctly stained dendrites were usually Sp8 positive and Tbx21 negative. Strangely, most of strongly NOS positive periglomerular cells with distinctly stained dendritic processes were Sp8 negative and Tbx21 negative. Thus Sp8 and Tbx21 immunoreactivities further characterized juxtaglomerular neurons and, especially confirmed the heterogeneity of NOS positive juxtaglomerular neurons.
    Neuroscience Research 02/2012; 73(1):24-31. DOI:10.1016/j.neures.2012.02.013 · 1.94 Impact Factor
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    ABSTRACT: Secretagogin is a six EF-hand calcium-binding protein that can identify granule cells in the dentate gyrus of hippocampus. The aim of this study was to determine if secretagogin can be detected in human blood cells. Eight adult males were recruited for blood analysis. Whole blood was separated into plasma, peripheral mononuclear cells and erythrocytes with Ficoll-Paque and probed for secretagogin using reverse-transcription polymerase chain reaction and Western blot. While secretagogin mRNA was detected in both peripheral mononuclear cells and erythrocytes using reverse-transcription polymerase chain reaction, SCGN protein was only detected in erythrocytes. Interestingly, peripheral mononuclear cells secretagogin mRNA expression levels showed significant negative correlation with age. This begets the question on the function of secretagogin in blood cells and if it is correlated to neurodegeneration associated with ageing. This remains our impetus for further research.
    Neuroscience Letters 08/2012; 526(1):59-62. DOI:10.1016/j.neulet.2012.08.006 · 2.03 Impact Factor
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