Neuronal Porosome Complex: Secretory Machinery at the Nerve Terminal
DISCOVERIES (ISSN 2359-7232), 2017, July-September issue
Submitted: June 4th, 2017; Revised: July 13th, 2017; Accepted: July 14th, 2017; Published: July 28th, 2017;
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Neuronal Porosome Complex: Secretory Machinery at the Nerve Terminal
Mzia G. Zhvania (1, 2,*), Nino Pochkidze (1, 2)
(1) Institute of Chemical Biology, Ilia State University, 3/5 K. Cholokhashvili Avenue, 0162, Tbilisi;
(2) Department of Brain Ultrastructure and Nanoarchitecture, I. Beriitashvili Center of Experimental BioMedicine, 14, Gotua Street, 0160 Tbilisi, Georgia;
*Corresponding author: Professor Mzia G. Zhvania,
Abstract
Neuronal porosomes are 15 nm cup-shaped lipoprotein secretory machines composed of nearly 30 proteins present at the presynaptic membrane, that have been investigated using multiple imaging modalities, such as electron microscopy, atomic force microscopy, and solution X-ray. Synaptic vesicles transiently dock and fuse at the base of the porosome cup facing the cytosol, by establishing a fusion pore for neurotransmitter release. Studies on the morphology, dynamics, isolation, composition, and reconstitution of the neuronal porosome complex provide a molecular understanding of its structure and function. In the past twenty years, a large body of evidence has accumulated on the involvement of the neuronal porosome proteins in neurotransmission and various neurological disorders. In light of these findings, this review briefly summarizes our current understanding of the neuronal porosome complex, the secretory nanomachine at the nerve terminal.
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References
1. Schneider SW, Sritharan KC, Geibel JP, Oberleithner H, Jena BP. Surface Dynamics in Living Acinar Cells Imaged by Atomic Force Microscopy: Identification of Plasma Membrane Structures Involved in Exocytosis, Proc. Natl. Acad. Sci. USA, 1997; 94: 316-321.
2. Jena BP, Cho SJ, Jeremic A, Stromer MH, Abu-Hamdah R. Structure and composition of the fusion pore. Biophys. J. 2003; 84: 1337-43.
3. Jeremic A, Kelly M, Cho S-J, et al. Reconstituted fusion pore. Biophys. J. 2003; 85:2035-43.
4. Cho S-J, Wakade A, Pappas GD, et al. New structure involved in transient membrane fusion and exocytosis. New York Academy of Science Annals. 2002; 971: 254-56.
5. Cho S-J, Jeftinija K, Glavaski A, et al. Structure and dynamics of the fusion pores in live GH-secreting cells revealed using atomic force microscopy. Endocrinology, 2002; 143: 1144-48.
6. Cho W-J, Jeremic A, Rognlien KT, et al. Structure, isolation, composition and reconstitution of the neuronal fusion pore. Cell Biol. Int. 2004; 28: 699-708.
7. Lee J-S, Jeremic A, Shin L, et al. Neuronal Porosome proteome: Molecular dynamics and architecture. J. Proteomics, 2012; 75:3 952-62.
8. Kovari LC, Brunzelle JS, Lewis KT, et al. X-ray solution structure of the native neuronal porosome-synaptic vesicle complex: Implication in neurotransmitter release. Micron, 2014; 56: 37-43.
9. Craciun C, Barbu-Tudoran L. Identification of new structural elements within ‘porosomes’ of the exocrine pancreas: a detailed study using high-resolution electron microscopy. Micron, 2013; 44:137-142
10. Drescher DG, Cho WJ, Drescher MJ. Identification of the porosome complex in the hair cell. Cell Biol. Int. Rep. 2011; 18:31-34.
11. Japaridze NJ, Okuneva VG, Qsovreli MG, et al. Hypokineitic stress and neuronal porosome complex in the rat brain: the electron microscopic study. Micron, 2012; 43, 9: 948-963.
12. Naik AR, Kulkarni SP, Lewis KT, et al. Functional reconstitution of the porosome complex in live cells. Endocrinology, 2016: 157 :54-60.
13. Almers W, Tse FW. Transmitter release from synapses: does a preassembled fusionpore initiate exocytosis? Neuron. 1990; 4: 813-18.
14. Neher E. Secretion without full fusion. Nature 1993; 363: 497–98.
15. Monck JR, Fernandez JM. The exocytotic fusion pore. J. Cell Biol. 1992; 119:1395-404.
16. Cho S-J, Kelly M, Rognlien KT, et al. SNAREs in opposing bilayers interacts in a circular array to form conducting pores. Biophys. J. 2002; 83: 2522-7.
17. Cho W-J, Jeremic A, Jena BP. Size of supramolecular SNARE complex: membrane-directed self-assembly. J. Am. Chem. Soc. 2005; 127: 10156-7.
18. Jeremic A, Quinn AS, Cho W-J, et al. Energy-dependent disassembly of self-assembled SNARE complex: observation at nanometer resolution using atomic force microscopy. J. Am. Chem. Soc. 2006; 128: 26-7.
19. Cook JD, Cho WJ, Stemmler TL, et al. Circular dichroism (CD) spectroscopy of the assembly and disassembly of SNAREs: the proteins involved in membrane fusion in cells. Chem. Phys. Lett. 2008; 462: 6-9.
20. Shin L, Cho W-J, Cook J, et al. Membrane lipids influence protein complex assembly-disassembly. J. Am. Chem. Soc. 2010; 132: 5596-7.
21. Cho WJ, Lee J-S, Ren G, et al. Membrane-directed molecular assembly of the neuronal SNARE complex. J. Cell. Mol. Med. 2011; 15: 31-7.
22. Jeremic A, Kelly M, Cho J-H, et al. Calcium drives fusion of SNARE-apposed bilayers. Cell Biol. Int. 2004; 28: 19-31.
23. Jeremic A, Cho W-J, Jena BP. Membrane fusion: what may transpire at the atomic level. J. Biol. Phys. & Chem. 2004; 4: 139-42.
24. Issa Z, Manke CW, Jena BP, at al. Ca2+ bridging of apposed phospholipid bilayer J. Phys. Chem. 2010; 114: 13249-54.
25. Trimble WS, Cowan DW, Scheller RH. VAMP-1: A synaptic vesicle-associated integral membrane protein. Proc. Natl. Acad. Sci. USA. 1988: 85: 4538-4542.
26. Bennett MK, Calakos N, Scheller RH. Syntaxin: A synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 1992; 257: 255-9.
27. Oyler GA, Higgins GA, Hart RA, et al. The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J. Cell Biol. 1989: 109: 3039-3052.
28. Weber T, Zemelman BV, McNew JA, et al. SNAREpins: minimal machinery for membrane fusion. Cell. 1998; 92: 759-772.
29. Finkelstein A, Zimmerberg J, Cohen FS. Osmotic swelling of vesicles: its role in the fusion of vesicles with planar phospholipid bilayer membranes and its possible role in exocytosis. Annu. Rev. Physiol. 1986: 48; 163–174.
30. Holz RW. The role of osmotic forces in exocytosis from adrenal chromaffin cells. Annu. Rev. Physiol. 1986; 48: 175–189.
31. Almers W. Exocytosis.Annu. Rev. Physiol.1990; 52: 607–624.
32. Fernandez JM, Villalon M, Verdugo P. Reversible condensation of mast cell secretory products in vitro. Biophys. J. 1991; 59: 1022–1027.
33. Curran MJ, Brodwick MS. Ionic control of the size of vesicle matrix of beige mouse mast cells. J. Gen. Physiol. 1991; 98: 771–790.
34. Monck JR, Oberhauser AF, Alverez de Toledo G, et al. Is swelling of the secretory granule matrix the force that dilates the exocytotic fusion pore? Biophys. J. 1991; 59: 39–47.
35. Alverez de Toledo G, Fernandez-Chacon R, Fernandez JM. Release of secretory products during transient vesicle fusion. Nature 1993; 363: 554–558.
36. Gasser KW, DiDomenico J, Hopfer U. Secretagogues activate chloride transport pathways in pancreatic zymge granules. Am. J. Physiol. 1988; 254: G93–G99.
37. Fuller CM, Eckhardt L, Schulz I. Ionic and osmotic dependence of secretion from permeabilised acin of the rat pancreas. Pflugers Arch. 1989; 413; 385–394.
38. Fuller CM, Deetjen HH, Piiper A, et al.Secretagogue and second messenger-activated Cl-permeabilities in isolated pancreatic zymogen granules. Pflugers Arch. 1989; 415: 29–36.
39. Gasser KW, Hopfer U. Chloride transport across the membrane of parotid secretory granules. Am. J. Physiol. Cell 1990; 259: C413–C420.
40. Thevenod F, Gasser KW, Hopfer U. Dual modulation of chloride conductance by nucleotides in pancreatic and parotid zymogen granules. Biochem. J. 1990; 272: 119– 126.
41. Piiper A, Plusczyk T, Eckhardt L. et al. Effects of cholecystokinin JMV-180 and GTP analogs on enzyme secretion from permeabilized acini and chloride conductance in isolated zymogen granules of the rat pancreas.Eur. J. Biochem. 1991; 197: 391-398.
42. Thevenod F, Chathadi KV, Jiang B, et al. ATP-sensitive K+ conductance I pancreatic zymogen granules: block by glyburide and activation by diazoxide.J. Memb. Biol. 1992; 129: 253–266.
43. Takuma T, Ichida T, Okumura K, et al. Effect of vallinomycin on osmotic lysis of zymogen granules and amylase exocytosis from parotid acini. Am. J. Physiol. 1993; G895–G901.
44. Thevenod F, Hildebrandt J-P, Striessnig J, et al. Chloride and potassium conductances of mouse pancreatic zymogen granules are inversely regulated by a approximately 80-kDa mdr1a gene product. J. Biol. Chem. 1996; 271; 3300–3305.
45. Jena BP, Schneider SW, Geibel JP, et al. Gi regulation of secretory vesicle swelling examined by atomic force microscopy. Proc. Natl. Acad. Sci, USA. 1997; 94: 13317-13322.
46. Cho S.-J, Sattar AKM, Jeong E-H, et al. Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles. Proc. Natl. Acad. Sci. USA.2002; 99: 4720-4724.
47. Shin L, Basi N, Lee J-S, et al. Involvement of vH+-ATPase in synaptic vesicle swelling. J. Neurosci. Res. 2010; 88: 95-101.
48. Lee J-S, Cho W-J, Shin L, et al. Involvement of cholesterol in synaptic vesicle swelling. Exp. Biol. Med. 2010; 235: 470-477.
49. Chen Z-H, Lee J-S, Shin L, et al. Involvement of β-adrenergic receptor in synaptic vesicle swelling and implication in neurotransmitter release. J. Cell. Mol. Med. 2011; 15: 572-576.
50. Kelly M, Cho W-J, Jeremic A, Abu-Hamdah R, et al. Vesicle swelling regulates content expulsion during secretion. Cell Biol. Int. 2014; 28: 709-716.
51. Cronshaw JN, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ. Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 2002; 158: 915–927.
52. Jensen TP, Filoteo AG, Knopfel T, et al. Presynaptic plasma membrane Ca2+ ATPase isoform 2a regulates excitatory synaptic transmission in rat hippocampal CA3. The Journal of Physiology 2007; 579: 85-99.
53. Garside ML, Tumer PR, Austen B, et al. Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum. Neuroscience 2009; 162: 383-395.
54. Geerlings A, Nunez E, Lopez-Corcuera B, et al. Calcium- and syntaxin 1-mediated trafficking of the neuronal glycine transporter GLYT2. J. Biol. Chem. 2001; 276: 17584-17590.
55. de Juan-Sanz J, Nunez E, Villarego-Lopez L. et al. Na+/K+-ATPase is a new interacting partner for the neuronal glycine transporter GlyT2 that downregulates its expression in vitro and in vivo. J Neurosci. 2013; 33: 14269-14281.
56. Empson RM, Akemann W, Knopfel T. The role of the calcium transporter protein plasma membrane calcium ATPase PMCA2 in cerebellar Purkinje neuron function. Functional Neurology 2010; 25: 53-158.
57. Dodson HC, Charalabapoulou M. PMCA2 mutation causes structural changes in the auditory system in deafwaddler mice. Journal of Neurocytology 2001; 30: 281-292.
58. Nemhauser I, Goldberg DJ. Structural effects in axoplasm of DNase I, an actin depolymerizer that blocks fast axonal transport. Brain Research 1985; 334: 47-58.
59. Klein ME, Younts TJ, Castillo PE et al. RNA-binding protein Sam68 controls synapse number and local beta-actin mRNA metabolism in dendrites. Proc Natl Acad Sci USA 2013; 110: 3125-3130.
60. Cole JC, Villa BR, Wilkinson RS. Disruption of actin impedes transmitter release in snake motor terminals. The Journal of Physiology 2000; 525: 579-586.
61. Khanna R, Zougman A, Stanley EF. A proteomic screen for presynaptic terminal N-type calcium channel (CaV2.2) binding partners. Journal of Biochemistry and Molecular Biology 2007; 40: 302-314.
62. Khanna R, Li Q, Bewersdorf J, et al. The presynaptic CaV2.2 channel-transmitter release site core complex. The European Journal of Neuroscience 2007; 26: 547-559.
63. Iino S, Kobayashi S, Maekawa S. Immunohistochemical localization of a novel acidic calmodulin-binding protein, NAP-22, in the rat brain. Neuroscience 1999; 91: 1435-1444.
64. Iino S, Maekawa S, Immunohistochemical demonstration of a neuronal calmodulin-binding protein, NAP-22, in the rat spinal cord. Brain research 1999; 834: 66-73.
65. Yamamoto Y, Sokawa Y, Maekawa S. Biochemical evidence for the presence of NAP-22, a novel acidic calmodulin binding protein, in the synaptic vesicles of rat brain. Neuroscience Letters 1997; 224: 127-130.
66. Jeremic A, Cho W-J, Jena BP. Cholesterol is critical to the integrity of neuronal porosome/fusion pore. Ultramicroscopy 2006; 106: 674-677.
67. Freeman, NL, Field J. Mammalian homolog of the yeast cyclase associated protein, CAP/Srv2p, regulates actin filament assembly. Cell Motility and the Cytoskeleton 2000; 45: 106-120.
68. Zhang H, Ghai P, Wu H, et al. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. The Journal of Biological Chemistry 2013; 288: 20966-20977.
69. Balestrino M, Young J, Aitken P. Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices. Brain Research 1999; 838: 37-44.
70. Scuri R, Lombardo P, Cataldo E, et al. Inhibition of Na+/K+ ATPase potentiates synaptic transmission in tactile sensory neurons of the leech. The European journal of neuroscience 2007; 25:59-167.
71. Sinclair LI, Tayler HM, Love S. Synaptic protein levels altered in vascular dementia. Neuropathology and Applied Neurobiology 2015; 41: 533-543.
72. Mukaetova-Ladinska EB, Xuereb JH, Garcia-Sierra F, et al. Lewy body variant of Alzheimer's disease: selective neocortical loss of t-SNARE proteins and loss of MAP2 and alpha-synuclein in medial temporal lobe. The Scientific World Journal 2009; 9:1463-1475.
73. Greber S, Lubec G, Cairns N, et al. Decreased levels of synaptosomal associated protein 25 in the brain of patients with Down syndrome and Alzheimer's disease. Electrophoresis 1999; 20: 928-934
74. Corradini I, Donzelli A, Antonucci F, Welzl H, et al. Epileptiform activity and cognitive deficits in SNAP-25 (+/-) mice are normalized by antiepileptic drugs. Cerebral cortex 2014; 24: 364-376.
75. McKee AG, Loscher JS, O'Sullivan NC, et al. AAV-mediated chronic over-expression of SNAP-25 in adult rat dorsal hippocampus impairs memory-associated synaptic plasticity. Journal of Neurochemistry 2010; 112:991-1004.
76. Wu MN, Fergestad T, Lloyd TE, et al. Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo. Neuron 1999; 23: 593-605.
77. Sutton RB, Fasshauer D, Jahn R, Brunger A.T. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 1998; 395: 347– 353.
78. Jeremic A, Cho W-J, Jena BP. Involvement of water channels in synaptic vesicle swelling. Exp. Biol. Med. 2005; 230: 674-680.
79. Ceccarelli B, Hurlbut WP, Mauro A. Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. Journal of Cell Biology 1973; 57: 499-524.80. Aravanis AM, Pyle JL, Tsien RW. Single synaptic vesicles fusing transiently and successively without loss of identity. Nature. 2003; 423: 643–647.
81. Zhvania MG, Bikashvili TZ, Japaridze NJ, Lazrishvili II, Ksovreli M. White noise and neuronal porosome complex: transmission electron microscopic study. Discoveries 2014, Jul-Sep; 2(3): e25. DOI: 10.15190/d.2014.17
82. Anderson LL. Recent Studies on the Insulin-Secreting Porosome Complex Provide Potential Therapeutic Applications in the Treatment of Diabetes. Discoveries 2015, Oct-Dec; 3(4): e51. DOI: 10.15190/d.2015.43
83. Kubori T, Marsushima Y, Najamura D, et al. Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science 1998; 280: 602-605.
84. Schraldt O, Marlovits TC. Three-dimensional model of Salmonella’s needle complex at subnanometer resolution. Science 2011; 33: 1192-1195.
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