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Molecular Diversity in Neurosecretion: Reflections on the Hypothalamo-Neurohypophysial System

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Abstract

1. The diversity of molecules involved in various aspects of neurosecretion, such asproprotein processing, axonal transport of large dense core vesicles (LDCVs), and regulated secretion, is discussed in the context of the hypothalamo-neurohypophysial system (HNS).

2. Recent studies have uncovered a family of at least seven processing enzymes known as proprotein convertases (PCs) which are involved in proteolytically cleaving protein precursors at paired basic amino acid motifs to yield biologically active peptides. Three of these, PC1(3), 2, and 5, are found in neurons and are involved in producing regulatedsecretory peptide products.

3. The axonal transport of LDCVs occurs on microtubule tracks by still unknown mechanisms. There are over 11 distinct kinesin-related molecules that have now beenidentified as possible microtubule motor candidates.

4. Calcium channels in the nervous system are known to be derived from at leastfive α-subunit and four β-subunit genes with multiple alternatively spliced isoforms in each case. These could account, in part, for the varied calcium currents found in the HNS.

5. The large number of proteins and isoforms now demonstrated to be involved inregulated secretion are discussed, with a focus on LDCV compositions and the synaptotag-min gene family.

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REFERENCES

  • Bajjalieh, S. M., and Scheller, R. H. (1995). The biochemistry of neurotransmitter secretion. J. Biol. Chem. 270:1971–1974.

    Google Scholar 

  • Bargmann, W., and Scharrer, E. (1951). The origin of the posterior pituitary hormones. Am. Sci. 39:255–279.

    Google Scholar 

  • Bark, I. C., and Wilson, M. C. (1994). Regulated fusion in neurons: Snapping together the details. Proc. Natl. Acad. Sci. USA 91:4621–4624.

    Google Scholar 

  • Bean, A. J., Zhang, X., and Hökfelt, T. (1994). Peptide secretion: What do we know? FASEB J. 8:630–638.

    Google Scholar 

  • Bean, B. P. (1989). Classes of calcium channels in vertebrate cells. Annu. Rev. Physiol. 51:367–384.

    Google Scholar 

  • Bement, W. M., Hasson, T., Wirth, J. A., Cheney, R. E., and Mooseker, M. S. (1994). Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. Proc. Natl. Acad. Sci. USA 91:6549–6553.

    Google Scholar 

  • Bennett, M. K., and Scheller, R. H. (1993). The molecular machinery for secretion is conserved from yeast to neurons. Proc. Natl. Acad. Sci. USA 90:2559–2563.

    Google Scholar 

  • Birch, N. P., Hakes, D. J., Dixon, J. E., and Mezey, E. (1994). Distribution and regulation of the candidate prohormone processing enzymes SPC2 and SPC3 in adult rat brain. Neuropeptides 27:307–322.

    Google Scholar 

  • Birnbaumer, L., Campbell, K. P., Catterall, W. A., Harpold, M. M., Hofmann, F., Horne, W. A., Mori, Y., Schwartz, A., Snutch, T. P., Tanabe, T., and Tsien, R. W. (1994). The naming of voltage-gated calcium channels. Neuron 13:505–506.

    Google Scholar 

  • Bittner, M. A., and Holz, R. W. (1993). Protein kinase C and clostridial neurotoxins affect discrete and related steps in the secretory pathway. Cell. Mol. Neurobiol. 13:649–664.

    Google Scholar 

  • Bondy, C. A., Whitnall, M. H., Brady, L. D., and Gainer, H. (1989). Coexisting peptides in hypothalamic neuroendocrine systems: Some functional implications. Cell. Mol. Neurobiol. 9:427–446.

    Google Scholar 

  • Brady, S. (1991). Molecular motors in the nervous system. Neuron 7:521–533.

    Google Scholar 

  • Brady, S. (1995). A kinesin medley: Biochemical and functional heterogeneity. Trends Cell Biol. 5:159–164.

    Google Scholar 

  • Brady, S., and Sperry, A. O. (1995). Biochemical and functional diversity of microtubule motors in the nervous system. Curr. Opin. Neurobiol. 5:551–558.

    Google Scholar 

  • Braks, J. A. M., and Martens, G. J. M. (1994). 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell 78:263–273.

    Google Scholar 

  • Braks, J. A. M., and Martens, G. J. M. (1995). The neuroendocrine chaperon 7B2 can enhance in vitro POMC cleavage by prohormone convertase PC2. FEBS Lett. 371:154–158.

    Google Scholar 

  • Brose, N., Petrenko, A. G., Südhof, T. C., and Jahn, R. (1992). Synaptotagmin: A Ca2+ sensor on the synaptic vesicle surface. Science 256:1021–1025.

    Google Scholar 

  • Brose, N., Hofmann, K., Hata, Y., and Südhof, T. C. (1995). Mammalian homologues of C. elegans unc-13 gene define novel family of C2-domain proteins. J. Biol. Chem. 270:25273–25280.

    Google Scholar 

  • Brownstein, M. J., and Mezey, E. (1986). Multiple chemical messengers in hypothalamic magnocellular neurons. Prog. Brain Res. 68:161–168.

    Google Scholar 

  • Burgoyne, R. D. (1995). Targeting the chromaffin cell. Trends Cell Biol. 5:471–473.

    Google Scholar 

  • Calakos, N., and Scheller, R. H. (1996). Synaptic vesicle biogenesis, docking, and fusion: A molecular description. Physiol. Rev. 76:1–29.

    Google Scholar 

  • Castel, M., Gainer, H., and Dellmann, H.-D. (1984). Neuronal secretory systems. Int. Rev. Cytol. 88:303–459.

    Google Scholar 

  • Castellano, A., Wei, X., Birnbaumer, L., and Perez-Reyes, E. (1993). Cloning and expression of a neuronal calcium channel β subunit. J. Biol. Chem. 268:12359–12366.

    Google Scholar 

  • Cazalis, M., Dayanithi, G., and Nordmann, J. J. (1987). Hormone release from isolated nerve endings of the rat neurohypophysis. J. Physiol. (London) 390:55–70.

    Google Scholar 

  • Chan, S. J., Oliva, A. A., Jr., La Mendola, J., Grens, A., Bode, H., and Steiner, D. F. (1992). Conservation of the prohormone convertase gene family inmetazoa: Analysis of cDNAs encoding a PC 3-like protein from hydra. Proc. Natl. Acad. Sci. USA 89:6678–6682.

    Google Scholar 

  • Cheney, R. E., Riley, M. A., and Mooseker, M. S. (1993). Phylogenetic analysis of the myosin superfamily. Cell Motil. Cytoskeleton 24:215–233.

    Google Scholar 

  • Day, R., Schäfer, M. K.-H., Watson, S. J., Chrétien, M., and Seidah, N. G. (1992). Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary. Mol. Endocrinol. 6:485–497.

    Google Scholar 

  • Day, R., Schäfer, M. K.-H., Watson, S. J., Chrétien, M., and Seidah, N. G. (1993). Region specific expression of furin mRNA in the rat brain. Neurosci. Lett. 149:27–30.

    Google Scholar 

  • Dayanithi, G., Martin-Moutot, N., Barlier, S., Colin, D. A., Kretz-Zaepfel, M., Couraud, F., and Nordmann, J. J. (1988). The calcium channel antagonist omega-conotoxin inhibits secretion from peptidergic nerve terminals. Biochem. Biophys. Res. Commun. 156:255–262.

    Google Scholar 

  • Dayanithi, G., Ahnert-Hilger, G., Weller, U., Nordmann, J. J., and Gratzl, M. (1990). Release of vasopressin from isolated permeabilized neurosecretory nerve terminals is blocked by the light chain of botulinium A toxin. Neuroscience 39:711–715.

    Google Scholar 

  • Dayanithi, G., Steicher, B., Höhne-Zell, B., Yamasaki, S., Binz, T., Weller, U., Niemann, H., and Gratzl, M. (1994). Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial nerve terminals. Neuroscience 58:423–431.

    Google Scholar 

  • deBree, F. M., and Burbach, J. P. (1998). Structure-function relationships of the vasopressin hormone domains. Cell. Mol. Neurobiol. 18:171–190.

    Google Scholar 

  • Dong, W., Marcinkiewicz, M., Vieau, D., Chrétien, M., Seidah, N. G., and Day, R. (1995). Distinct mRNA expression of the highly homologous convertases PC5 and PACE4 in the rat brain and pituitary. J. Neurosci. 15:1778–1796.

    Google Scholar 

  • Dunlap, K., Luebke, J. I., and Turner, T. J. (1995). Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci. 18:89–98.

    Google Scholar 

  • Eberwine, J., Yeh, H., Miyashiro, K., Cao, Y., Nair, S., Finnel, R., Zettel, M., and Coleman, P. (1992). Analysis of gene expression in single live neurons. Proc. Natl. Acad. Sci. USA 89:3010–3014.

    Google Scholar 

  • Egger, E., Kirchmair, R., Kapelari, S., Hogue-Angeletti, R., and Winkler, H. (1994). Bovine posterior pituitary: Presence of p65 (synaptotagmin), PC1, PC2, and secretoneurin in large dense core vesicles. Neuroendocrinology 59:169–175.

    Google Scholar 

  • Eipper, B. A., Stoffers, D. A., and Mains, R. E. (1992). The biosynthesis of neuropeptides: Peptide α-amidation. Annu. Rev. Neurosci. 15:57–85.

    Google Scholar 

  • Elluru, R. G., Bloom, G., and Brady, S. T. (1995). Fast axonal transport of kinesin in the rat visual system: Functionality of kinesin heavy chain isoforms. Mol. Biol. Cell 6:21–40.

    Google Scholar 

  • Fink, D. J., Russell, J. T., Gainer, H., Brownstein, M. J., and Baumgold, J. (1981). Multiple-rate components of axonally transported proteins in the hypothalamo-neurohypophysial system of the rat. J. Neurobiol. 12:487–503.

    Google Scholar 

  • Fisher, T. E., and Bourque, C. W. (1996). Calcium channel subtypes in the somata and axon terminals of magnocellular neurosecretory cells. Trends Neurosci. 19:440–444.

    Google Scholar 

  • Foran, P., Lawrence, G. W., Shone, C. C., Foster, K. A., and Dolly, J. O. (1996). Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: Correction with its blockage of catecholamine release. Biochemistry 35:2630–2636.

    Google Scholar 

  • Fricker, L. D. (1988). Carboxypetidase E. Annu. Rev. Physiol. 50:309–321.

    Google Scholar 

  • Fricker, L. D. (ed.) (1991). Peptide Biosynthesis and Processing CRC Press, Boca Raton, FL.

    Google Scholar 

  • Fuller, R. S., Sterne, R. E., and Thorner, J. (1988). Enzymes required for yeast prohormone processing. Annu. Rev. Physiol. 50:345–362.

    Google Scholar 

  • Fuller, R. S., Brake, A. J., and Thorner, J. (1989). Intracellular targeting and structural conservation of a prohormone-processing protease. Science 246:482–486.

    Google Scholar 

  • Gainer, H. (1993). Intracellular protein trafficking and proprotein processing: An overview. In Loh, Y. P. (ed.), Mechanisms of Intracellular Trafficking and Processing of Pro-proteins CRC Press, Boca Raton, FL, pp. 1–17.

    Google Scholar 

  • Gainer, H., and Wray, S. (1994). The cellular and molecular biology of oxytocin and vasopressin. In Knobil, E., and Neill, J. D. (eds.), Physiology of Reproduction 2nd Ed., Raven Press, New York, pp. 1099–1129.

    Google Scholar 

  • Gainer, H., Russell, J. T., and Loh, Y. P. (1985). The enzymology and intracellular organization of peptide precursor processing: The secretory vesicle hypothesis. Neuroendocrinology 40:171–184.

    Google Scholar 

  • Gainer, H., Sarne, Y., and Brownstein, M. J. (1977a). Neurophysin biosynthesis: Conversion of a putative precursor during axonal transport. Science 195:1354–1356.

    Google Scholar 

  • Gainer, H., Sarne, Y., and Brownstein, M. J. (1977b). Biosynthesis and axonal transport of rat neurohypophysial proteins and peptide. J. Cell Biol. 73:366–381.

    Google Scholar 

  • Geppert, M., Goda, Y., Hammer, R. E., Li, C., Rosahl, T. W., Stevens, C. F., and Südhof, T. C. (1994). Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse. Cell 79:717–727.

    Google Scholar 

  • Goodson, H. V., Kang, S. J., and Endow, S. A. (1994). Molecular phylogeny of the kinesin family of microtubule motor proteins. J. Cell Sci. 107:1875–1884.

    Google Scholar 

  • Halpern, J. L., Habig, W. H., Trenchard, H., and Russell, J. T. (1990). Effect of tetanus toxin on oxytocin and vasopressin release from nerve endings of the neurohypophysis. J. Neurochem. 55:2072–2078.

    Google Scholar 

  • Hammer, J. A. (1994). The structure and function of unconventional myosins: A review. J. Muscle Res. Cell Motil. 15:1–10.

    Google Scholar 

  • Hasson, T., and Mooseker, M. S. (1996). Vertebrate unconventional myosins. J. Biol. Chem. 271:16431–16434.

    Google Scholar 

  • Hirokawa, N. (1996). Organelle transport along microtubules—the role of KIFs. Trends Cell Biol. 6:135–141.

    Google Scholar 

  • Hofmann, F., Biel, V., and Flockerzi, V. (1994). Molecular basis for Ca2+ channel diversity. Annu. Rev. Neurosci. 17:399–418.

    Google Scholar 

  • Holz, R. W., Brondy, W. H., Senter, R. A., Kuizon, L., and Macara, I. G. (1994). Evidence for the involvement of Rab 3A in Ca2+-dependent exocytosis from adrenal chromaffin granules. J. Biol. Chem. 269:10229–10234.

    Google Scholar 

  • Huang, L.-Y. M., and Neher, E. (1996). Ca2+-dependent exocytosis in the somata of dorsal root ganglion neurons. Neuron 17:135–145.

    Google Scholar 

  • Hulin, R., Singer-Lahat, D., Freichel, M., Biel, M., Dascal, N., Hofmann, F., and Flockerzi, V. (1993). Calcium channel β subunit heterogeneity: Functional expression of cloned cDNA from heart, aorta, and brain. EMBO J. 11:885–890.

    Google Scholar 

  • Hutton, J. C. (1992). Subtilisin-like proteases involved in the activation of proproteins of the eukaryotic secretory pathway. Cell Biol. 2:1131–1142.

    Google Scholar 

  • Jackson, M. (1995). Presynaptic excitability. Int. Rev. Neurobiol. 38:201–251.

    Google Scholar 

  • Jacobsson, G., and Meister, B. (1996). Molecular components of the exocytotic machinery in the rat pituitary gland. Endocrinology 137:5344–5356.

    Google Scholar 

  • Jahn, R., and Südhof, T. C. (1994). Synaptic vesicles and exocytosis. Annu. Rev. Neurosci. 17:219–246.

    Google Scholar 

  • Jorgansen, A., Fjalland, B., Christensen, J. D., and Treiman, M. (1994). Dihydropyridine ligands influence the evoked release of oxytocin and vasopressin dependent on stimulation conditions. Eur. J. Pharmacol. 259:157–163.

    Google Scholar 

  • Jurguitis, P., Shuang, R., Fletcher, A., and Stuenkel, E. L. (1996). Characterization and distribution of SNARE proteins at neuroendocrine nerve endings. Neuroendocrinology 64:379–392.

    Google Scholar 

  • Kato, M. C., Chapman, C., and Bicknell, R. J. (1992). Activation of K-opioid receptors inhibits depolarization-evoked exocytosis but not the rise in intracellular Ca2+ in secretory nerve terminals of the neurohypophysis. Brain Res. 574:138–146.

    Google Scholar 

  • Kelly, R. B. (1995). Synaptotagmin is just a calcium sensor. Curr. Biol. 5:257–259.

    Google Scholar 

  • Kim, H.-L., Kim, H., Lee, P., King, R. G., and Chin, H. (1992). Rat brain expresses an alternatively spliced form of the dihydropyridine-densitive L-type calcium channel α2 subunit. Proc. Natl. Acad. Sci. USA 89:3251–3255.

    Google Scholar 

  • Kreis, T., and Vale, R. (eds.) (1994). Guidebook to the Cytoskeletal and Motor Proteins Oxford University Press, Oxford, p. 276.

    Google Scholar 

  • Kreutzberg, G. W. (1969). Neuronal dynamics and axonal flow. IV. Blockage of intraaxonal transport by colchicine. Proc. Natl. Acad. Sci. USA 62:722–728.

    Google Scholar 

  • Kumar, J., Yu, H., and Sheetz, M. P. (1995). Kinectin, an essential anchor for kinesin-driven vesicle motility. Science 267:1834–1837.

    Google Scholar 

  • Langford, G. M. (1995). Actin-and microtubule-dependent organelle motors: Interrelationships between the two motility systems. Curr. Opin. Cell Biol. 7:82–88.

    Google Scholar 

  • Lemos, J. R., Wang, G., Wang, X., Stuenkel, E. J., Nordmann, J. J., and Triestman, S. N. (1994). Effects of toxins on Ca2+ currents and peptide release from nerve terminals. Ann. N.Y. Acad. Sci. 710:11–29.

    Google Scholar 

  • Littleton, J. T., and Bellen, H. J. (1995) Synaptotagmin controls and modulates synaptic-vesicle fusion in a Ca2+-dependent manner. Trends Neurosci. 18:177–183.

    Google Scholar 

  • Loh, Y. P. (ed.) (1993). Mechanisms of Intracellular Trafficking and Processing of Proproteins CRC Press, Boca Raton, FL.

    Google Scholar 

  • Mains, R. E. Dickerson, I. M., May, V., Stoffers, D. A., Perkins, S. N. Ouafik, L., Husten, E. J., and Eipper, B. A. (1990). Cellular and molecular aspects of peptide hormone biosynthesis. Front. Neuroendocrinol. 11:52–89.

    Google Scholar 

  • Martens, G. J. M., Braks, J. A. M., Eib, D. W., Zhou, Y., and Lindberg, I. (1994). The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2. Proc. Natl. Acad. Sci. USA 91:5484–5787.

    Google Scholar 

  • Martin, K. C., Hu, Y., Armitage, B. A., Siegelbaum, S. A., Kandel, E. R., and Kaang, B.-K. (1995). Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons. Proc. Natl. Acad. Sci. USA 92:11307–11311.

    Google Scholar 

  • Martin, T. F. J. (1994). The molecular machinery for fast and slow secretion. Curr. Opin. Neurobiol. 4:626–632.

    Google Scholar 

  • Matteoli, M., Haimann, C., Torri-Tarelli, F., Polak, J. M., Ceccarelli, B., and DeCamilli, P. (1988). Differential effect of latrotoxin on exocytosis of Ach-containing small synaptic vesicles and CGRP-containing large dense core vesicles at the frog neuromuscular junction. Proc. Natl. Acad. Sci. USA 85:7366–7370.

    Google Scholar 

  • McCleskey, E. W. (1994). Calcium channels: Cellular roles and molecular mechanisms. Curr. Opin. Neurobiol. 4:304–312.

    Google Scholar 

  • Mizuta, M., Inagaki, N., Nemoto, Y., Matsukura, S., Takahashi, M., and Seino, S. (1994). Synaptotagmin III is a novel isoform of rat synaptotagmin expressed in endocrine and neuronal cells. J. Biol. Chem. 269:11675–11678.

    Google Scholar 

  • Montecucco, C., and Schiavo, G. (1995). Structure and function of tetanus and botulinum neurotoxins. Q. Rev. Biophys. 28:423–472.

    Google Scholar 

  • Monyer, H., and Lambolez, B. (1995). Molecular biology and physiology at the single-cell level. Curr. Opin. Neurobiol. 5:383–387.

    Google Scholar 

  • Mooseker, M. S., and Cheney, R. E. (1995). Unconventional myosins. Annu. Rev. Cell. Dev. Biol. 11:633–675.

    Google Scholar 

  • Mori, Y., Friedrich, T., Kim, M. S., Mikami, A., Nakai, J., Ruth, P., Bosse, E., Hofmann, F., Flockerzi, V., Furuichi, T., Mishikiba, K., Imoto, K., Tanabe, T., and Numa, S. (1991). Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398–402.

    Google Scholar 

  • Neher, E., and Zucker, R. S. (1993). Multiple calcium-dependent processes related to secretion in bovine chromaffin cells. Neuron 10:21–30.

    Google Scholar 

  • Nowycky, M. C., Seward, E. P., and Chernevskaya, N. I. (1998). Excitation-secretion coupling in mammalian neurohypophysial nerve terminals. Cell. Mol. Neurobiol. 18:65–80.

    Google Scholar 

  • Parish, D. C., Rodriguez, E. M., Birkett, S. D., and Pickering, B. T. (1981). Effects of small doses of colchicine on the components of the hypothalamo-neurohypophysial system of the rat. Cell Tissue Res. 220:809–827.

    Google Scholar 

  • Pereira, A., and Goldstein, L. S. B. (1994). The kinesin superfamily. In Hyams, J. S., and Lloyd, C. W. (eds.), Microtubules Wiley-Liss, New York, pp. 269–286.

    Google Scholar 

  • Perez-Reyes, E., Wei, X., Castellano, A., and Birnbaumer, L. (1990). Molecular diversity of L-type calcium channels. J. Biol. Chem. 265:20430–20436.

    Google Scholar 

  • Popov, S. V., and Poo, M.-M. (1993). Synaptotagmin: A calcium-sensitive inhibitor of exocytosis? Cell 73:1247–1249.

    Google Scholar 

  • Puro, D. G., Hwang, J.-J., Kwon, O.-J., and Chin, H. (1996). Characterizations of an L-type calcium channel expressed by human retinal Müller (glial) cells. Mol. Brain Res. 37:41–48.

    Google Scholar 

  • Reuter, H. (1996). Diversity and function of presynaptic calcium channels in the brain. Curr. Opin. Neurobiol. 6:331–337.

    Google Scholar 

  • Rouille, Y., Duguay, S. J., Lund, K., Furuta, M., Gong, Q., Lipkind, G., Oliva, A. A., Jr., Chan, S. J., and Steiner, D. F. (1995). Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: The subtilisin-like proprotein convertases. Front. Neuroendocrinol. 16:322–361.

    Google Scholar 

  • Sano, Y. (1985). History of neurosecretion. In Kobayashi, H., Bern, A. A., and Urano, A. (eds.), Neurosecretion and the Biology of Neuropeptides, Springer-Verlag, Berlin, pp. 1–7.

    Google Scholar 

  • Sather, W. A., Tanabe, T., Zhang, J. F., Mori, Y., Adams, M. E., and Tsien, R. W. (1993). Distinctive biophysical and pharmacological properties of class A (Bl) calcium channel alpha 1 subunits. Neuron 11:291–303.

    Google Scholar 

  • Schäfer, M. K.-H., Stoffers, D. A., Eipper, B. A., and Watson, S. J. (1992). Expression of peptidylglycine α-amidating monooxygenase (EC1.14.17.3) in the rat central nervous system. J. Neurosci. 12:222–234.

    Google Scholar 

  • Schäfer, M. K.-H., Day, R., Cullinan, W. E., Chrétien, M., Seidah, N. G., and Watson, S. J. (1993). Gene expression of prohormone and proprotein convertases in the rat CNS: A comparative in situ hybridization analysis. J. Neurosci. 13:1258–1279.

    Google Scholar 

  • Seidah, N. G., and Chrétien, M. (1992). Pro-protein and pro-hormone convertases of the subtilism family. Recent developments and future perspectives. Trends Endocrinol. Metab. 3:133–140.

    Google Scholar 

  • Seidah, N. G., Day, R., and Chrétien, M. (1993a). The family of pro-hormone and pro-protein convertases. Biochem. Soc. Trans. 21:685–691.

    Google Scholar 

  • Seidah, N. G., Day, R., Marcinkiewicz, M., and Chrétien, M. (1993b). Mammalian paired basic amino acid convertases of prohormones and proproteins. Ann N.Y. Acad. Sci. 680:135–146.

    Google Scholar 

  • Seidah, N. G., Chrétien, M., and Day, R. (1994). The family of subtilisin/kexin-like pro-protein and pro-hormone convertases: Divergent or shared functions. Biochimie 76:197–209.

    Google Scholar 

  • Seidah, N. G., hanelin, J., Mamarbachi, M., Dong, W., Tadros, H., Mbikay, M., Chrétien, M., and Day, R. (1996). cDNA structure, tissue distribution, and chromosomal localization of rat PC 7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases. Proc. Natl. Acad. Sci. USA 93:3388–3393.

    Google Scholar 

  • Seward, E. P., and Nowycky, M. C. (1996). Kinetics of stimulus-coupled secretion in dialyzed bovine chromaffin cells in response to trains of depolarizing pulses. J. Neurosci. 16:553–562.

    Google Scholar 

  • Seward, E. P., Chernevskaya, N. I., and Nowycky, M. C. (1995). Exocytosis in peptidergic nerve terminals exhibits two calcium sensitive phases during pulsatile calcium entry. J. Neurosci. 15:3390–3399.

    Google Scholar 

  • Seward, E. P., Chernevskays, N. I., and Nowycky, M. C. (1996). Ba2+ ions evoke two kinetically distinct patterns of exocytosis in chromaffin cells, but not in neurohypophysial nerve terminals. J. Neurosci. 16:1370–1379.

    Google Scholar 

  • Smith, I. A. (ed.) (1995). Peptidases and Neuropeptide Processing, Methods in Neurosciences, Vol. 23, Academic Press, San Diego.

    Google Scholar 

  • Söllner, T., Whiteheart, S. W., Brunner, M., Erdjument-Bromage, H., Geromanos, S., Tempst, P., and Rothman, J. E. (1993). SNAP receptors implicated in vesicle targeting and fusion. Nature (Lond.) 362:318–324.

    Google Scholar 

  • Steiner, D. F. (1991). The biosynthesis of biologically active peptides: A perspective. In Fricker, L. D. (ed.), Peptide Biosynthesis and Processing, CRC Press, Boca Raton, FL, Chap. 1.

    Google Scholar 

  • Steiner, D. F., Smeekens, S. P., Ohagai, S., and Chan, S. J. (1992). The new enzymology of precursor processing endoproteases. J. Biol. Chem. 267:23435–23438.

    Google Scholar 

  • Südhof, T. C. (1995). The synaptic vesicle cycle: A cascade of protein-protein interactions. Nature 375:645–653.

    Google Scholar 

  • Südhof, T. C., and Rizo, J. (1996). Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron 17:379–388.

    Google Scholar 

  • Ullrich, B., Ushkaryov, Y. A., and Südhof, T. C. (1995). Cartography of neurexins: More than 1,000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14:497–507.

    Google Scholar 

  • Vallee, R. B., and Sheetz, M. P. (1996). Targeting of motor proteins. Science 271:1539–1544.

    Google Scholar 

  • Von Spreckelson, S., Lollike, K., and Treimars, M. (1990). Ca2+ and vasopressin release in isolated neurohypophysis: Differential effects of four classes of Ca2+ channel ligands. Brain Res. 514:68–76.

    Google Scholar 

  • Wagner, M. C., Pfister, K. K., Bloom, G. S., and Brady, S. T. (1989). Copurification of kinesin polypeptides with microtubule-stimulated Mg-ATPaseactivity and kinetic analysis of enzymatic processes. Cell Motil. Cytoskeleton 12:195–215.

    Google Scholar 

  • Walch-Solimena, C., Takei, K., Marek, K. L., Südhof, T. C., DeCamilli, P., and Jahn, R. (1993). Synaptotagmin: A membrane constituent of neuropeptide-containing large dense core vesicles. J. Neurosci. 13:3895–3903.

    Google Scholar 

  • Waller, S. J., Ratty, A., Burbach, J. P., and Murphy, D. (1998). Transgenic and transcriptional studies on neurosecretory cell gene expression. Cell. Mol. Neurobiol. 18:149–172.

    Google Scholar 

  • Wang, X., Triestman, S. N., and Lemos, J. R. (1993). Single channel recordings of N-type and L-type Ca2+ currents in rat neurohypophysial terminals. J. Neurophysiol. 70:1617–1628.

    Google Scholar 

  • Wheeler, M. B., Sheu, L., Ghai, M., Bouquillon, A., Grondin, G., Weller, U., Beaudoin, A. R., Bennett, M., Trimble, W. S., and Gaisano, H. Y. (1996). Characterization of SNARE protein expression in β-cell lines and pancreatic islets. Endocrinology 137:1340–1348.

    Google Scholar 

  • Williams, M. E., Feldman, D. H., McCue, A. F., Brenner, R., Velicelbi, G., Elis, S. B., and Harpold, M. M. (1992). Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype. Neuron 8:71–84.

    Google Scholar 

  • Williams, M. E., Marubio, L. M., Deal, C. R., Hans, M., Brust, P. F., Philipson, L. H., Miller, R. J., Johnson, E. C., Harpold, M. M., and Elis, S. B. (1994). Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. J. Biol. Chem. 269:22347–22357.

    Google Scholar 

  • Winkler, H., and Fischer-Colbrie, R. (1998). Regulation of the biosynthesis of large dense-core vesicles in chromaffin cells and neurons. Cell. Mol. Neurobiol. 18:193–210.

    Google Scholar 

  • Yu, H., Nicchita, C. V., Kumar, J., Becker, M., Toyoshima, I., and Sheetz, M. P. (1995). Characterization of kinectin, a kinesin binding protein: Primary sequence and N-terminal topogenic signal analysis. Mol. Biol. Cell 6:171–183.

    Google Scholar 

  • Zhang, J. F., Randall, A. D., Ellinor, P. T., Horne, W. A., Sather, W. A., Tanabe, T., Schwartz, T. L., and Tsien, R. W. (1993). Distinctive pharmacology and kinetics of cloned Ca2+ channels and their counterparts in mammalian CNS neurons. Neuropharmacology 32:1075–1088.

    Google Scholar 

  • Zheng, M., Streck, R. D., Scott, R. E. M., Seidah, N. G., and Pintar, J. E. (1994). The developmental expression in rat of proteases furin, PC1, PC2, and carboxypeptidase E: Implications for early maturation of proteolytic processing capacity. J. Neurosci. 14:4656–4673.

    Google Scholar 

  • Zhu, X., and Lindberg, I. (1995). 7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. J. Cell Biol. 129:1641–1650.

    Google Scholar 

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Gainer, H., Chin, H. Molecular Diversity in Neurosecretion: Reflections on the Hypothalamo-Neurohypophysial System. Cell Mol Neurobiol 18, 211–230 (1998). https://doi.org/10.1023/A:1022568904002

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