title: A family of Ca2+-dependent activator proteins for secretion: comparative analysis of structure, expression, localization, and function.
abstract: Ca2+-dependent activator protein for secretion (CAPS) 1 is an essential cytosolic component of the protein machinery involved in large dense-core vesicle (LDCV) exocytosis and in the secretion of a subset of neurotransmitters. In the present study, we report the identification, cloning, and comparative characterization of a second mammalian CAPS isoform, CAPS2. The structure of CAPS2 and its function in LDCV exocytosis from PC12 cells are very similar to those of CAPS1. Both isoforms are strongly expressed in neuroendocrine cells and in the brain. In subcellular fractions of the brain, both CAPS isoforms are enriched in synaptic cytosol fractions and also present on vesicular fractions. In contrast to CAPS1, which is expressed almost exclusively in brain and neuroendocrine tissues, CAPS2 is also expressed in lung, liver, and testis. Within the brain, CAPS2 expression seems to be restricted to certain brain regions and cell populations, whereas CAPS1 expression is strong in all neurons. During development, CAPS2 expression is constant between embryonic day 10 and postnatal day 60, whereas CAPS1 expression is very low before birth and increases after postnatal day 0 to reach a plateau at postnatal day 21. Light microscopic data indicate that both CAPS isoforms are specifically enriched in synaptic terminals. Ultrastructural analyses show that CAPS1 is specifically localized to glutamatergic nerve terminals. We conclude that at the functional level, CAPS2 is largely redundant with CAPS1. Differences in the spatial and temporal expression patterns of the two CAPS isoforms most likely reflect as yet unidentified subtle functional differences required in particular cell types or during a particular developmental period. The abundance of CAPS proteins in synaptic terminals indicates that they may also be important for neuronal functions that are not exclusively related to LDCV exocytosis.
authors.affiliation: Department of Molecular Neurobiology, Max-Planck-Institute for Experimental Medicine and Deutsche Forschungsgemeinschaft Center for Molecular Physiology of the Brain, D-37075 Göttingen, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Speidel
authors.forename: Frederique
authors.initials: F
authors.lastname: Varoqueaux
authors.forename: Carsten
authors.initials: C
authors.lastname: Enk
authors.forename: Mari
authors.initials: M
authors.lastname: Nojiri
authors.forename: Ruslan N
authors.initials: RN
authors.lastname: Grishanin
authors.forename: Thomas F J
authors.initials: TF
authors.lastname: Martin
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013737:Testis / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D033921:Vesicular Transport Proteins
chemical_list: C409027:CADPS protein, human; C449654:CAPS2 protein, human; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D002118:Calcium