Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion.
Vyšlo v časopise: RIC-7 Promotes Neuropeptide Secretion. PLoS Genet 8(1): e32767. doi:10.1371/journal.pgen.1002464 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002464
1. BurgoyneRDMorganA 2003 Secretory granule exocytosis. Physiol Rev 83 581 632
2. SudhofTC 2004 The synaptic vesicle cycle. Annu Rev Neurosci 27 509 547
3. WeimerRMRichmondJEDavisWSHadwigerGNonetML 2003 Defects in synaptic vesicle docking in unc-18 mutants. Nat Neurosci 6 1023 1030
4. VoetsTToonenRFBrianECde WitHMoserT 2001 Munc18-1 promotes large dense-core vesicle docking. Neuron 31 581 591
5. HammarlundMPalfreymanMTWatanabeSOlsenSJorgensenEM 2007 Open syntaxin docks synaptic vesicles. PLoS Biol 5 e198
6. HammarlundMWatanabeSSchuskeKJorgensenEM 2008 CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons. J Cell Biol 180 483 491
7. de WitHCornelisseLNToonenRFVerhageM 2006 Docking of secretory vesicles is syntaxin dependent. PLoS One 1 e126
8. KlenchinVAMartinTF 2000 Priming in exocytosis: attaining fusion-competence after vesicle docking. Biochimie 82 399 407
9. MartinTF 2002 Prime movers of synaptic vesicle exocytosis. Neuron 34 9 12
10. JenaBP 2005 Cell secretion and membrane fusion. Domest Anim Endocrinol 29 145 165
11. SorensenJB 2005 SNARE complexes prepare for membrane fusion. Trends Neurosci 28 453 455
12. VoetsTMoserTLundPEChowRHGeppertM 2001 Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I. Proc Natl Acad Sci U S A 98 11680 11685
13. EdwardsRH 1998 Neurotransmitter release: variations on a theme. Curr Biol 8 R883 885
14. KimTGondre-LewisMCArnaoutovaILohYP 2006 Dense-core secretory granule biogenesis. Physiology (Bethesda) 21 124 133
15. BrunsDJahnR 1995 Real-time measurement of transmitter release from single synaptic vesicles. Nature 377 62 65
16. GrishaninRNKowalchykJAKlenchinVAAnnKEarlesCA 2004 CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2 binding protein. Neuron 43 551 562
17. BerwinBFloorEMartinTF 1998 CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron 21 137 145
18. SpeeseSPetrieMSchuskeKAilionMAnnK 2007 UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. J Neurosci 27 6150 6162
19. JockuschWJSpeidelDSiglerASorensenJBVaroqueauxF 2007 CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins. Cell 131 796 808
20. SieburthDMadisonJMKaplanJM 2007 PKC-1 regulates secretion of neuropeptides. Nat Neurosci 10 49 57
21. KangLHeZXuPFanJBetzA 2006 Munc13-1 is required for the sustained release of insulin from pancreatic beta cells. Cell Metab 3 463 468
22. MillerKGAlfonsoANguyenMCrowellJAJohnsonCD 1996 A genetic selection for Caenorhabditis elegans synaptic transmission mutants. Proc Natl Acad Sci U S A 93 12593 12598
23. NguyenMAlfonsoAJohnsonCDRandJB 1995 Caenorhabditis elegans mutants resistant to inhibitors of acetylcholinesterase. Genetics 140 527 535
24. SieburthDCh'ngQDybbsMTavazoieMKennedyS 2005 Systematic analysis of genes required for synapse structure and function. Nature 436 510 517
25. JacobTCKaplanJM 2003 The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions. J Neurosci 23 2122 2130
26. BaiJHuZDittmanJSPymECKaplanJM 2010 Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell 143 430 441
27. VashlishanABMadisonJMDybbsMBaiJSieburthD 2008 An RNAi screen identifies genes that regulate GABA synapses. Neuron 58 346 361
28. MullenGPMathewsEASaxenaPFieldsSDMcManusJR 2006 The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA transporter required for clearance of synaptic GABA. Mol Biol Cell 17 3021 3030
29. DittmanJKaplanJ 2006 Factors regulating the abundance and localization of Synaptobrevin in the plasma membrane. PNAS 103 11399 404
30. Ch'ngQSieburthDKaplanJM 2008 Profiling synaptic proteins identifies regulators of insulin secretion and lifespan. PLoS Genet 4 e1000283
31. HuZPymECBabuKVashlishan MurrayABKaplanJM 2011 A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron 71 92 102
32. JanssenTMeelkopELindemansMVerstraelenKHussonSJ 2008 Discovery of a cholecystokinin-gastrin-like signaling system in nematodes. Endocrinology 149 2826 2839
33. LiWFengZSternbergPWXuXZ 2006 A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. Nature 440 684 687
34. JorgensenEM 2005 Gaba. WormBook 1 13
35. MahoneyTRLuoSRoundEKBraunerMGottschalkA 2008 Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans. Proc Natl Acad Sci U S A 105 16350 16355
36. AugustinIRosenmundCSudhofTCBrose 1999 Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles [In Process Citation]. Nature 400 457 461
37. KaeserPSDengLChavezAELiuXCastilloPE 2009 ELKS2alpha/CAST deletion selectively increases neurotransmitter release at inhibitory synapses. Neuron 64 227 239
38. MartinJAHuZFenzKMFernandezJDittmanJS 2011 Complexin has opposite effects on two modes of synaptic vesicle fusion. Curr Biol 21 97 105
39. HobsonRJLiuQWatanabeSJorgensenEM 2011 Complexin maintains vesicles in the primed state in C. elegans. Curr Biol 21 106 113
40. XuTXuP 2008 Searching for molecular players differentially involved in neurotransmitter and neuropeptide release. Neurochem Res 33 1915 1919
41. BrennerS 1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94
42. LacknerMRNurrishSJKaplanJM 1999 Facilitation of synaptic transmission by EGL-30 Gqalpha and EGL-8 PLCbeta: DAG binding to UNC-13 is required to stimulate acetylcholine release. Neuron 24 335 346
43. BurbeaMDreierLDittmanJSGrunwaldMEKaplanJM 2002 Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans. Neuron 35 107 120
44. DittmanJSKaplanJM 2006 Factors regulating the abundance and localization of synaptobrevin in the plasma membrane. Proc Natl Acad Sci U S A 103 11399 11404
45. RichmondJEJorgensenEM 1999 One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction. Nat Neurosci 2 791 797
46. MelloCCKramerJMStinchcombDAmbrosV 1991 Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. Embo J 10 3959 3970
47. FireA 1997 Fire Vector Kit. In Addgene Inc Cambridge: USA
48. SimonDJMadisonJMConeryALThompson-PeerKLSoskisM 2008 The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions. Cell 133 903 915
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