title: The renaissance of Ca2+-binding proteins in the nervous system: secretagogin takes center stage.
abstract: 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.
authors: European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; Division of Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
authors: Alán
authors: A
authors: Alpár
authors: Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom.
authors: Johannes
authors: J
authors: Attems
authors: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, Tomtebodavägen 23A, S-17165 Solna, Sweden.
authors: Jan
authors: J
authors: Mulder
authors: Department of Neuroscience, Retzius väg 8, Karolinska Institutet, S-17177 Stockholm, Sweden.
authors: Tomas
authors: T
authors: Hökfelt
authors: European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; Division of Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden. Electronic address: Tibor.Harkany@ki.se.
authors: Tibor
authors: T
authors: Harkany
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009490:Neurosecretory Systems / Q000196:embryology / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064046:Secretagogins; D015398:Signal Transduction / Q000502:physiology*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D020033:Protein Isoforms; D064046:Secretagogins; D006899:Mixed Function Oxygenases; C519811:NECAB1 protein, human; D002118:Calcium