Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction
Synapse development is initiated by genetic programs, but is coordinated by neuronal activity, by communication between the pre- and postsynaptic compartments, and by cellular signals that integrate the status of the whole organisms and its developmental progression. The molecular mechanisms underlining these processes are poorly understood. In particular, how neurotransmitter receptors are recruited and stabilized at central synapses remain the subject of intense research. The Drosophila NMJ is a glutamatergic synapse similar in composition and physiology with mammalian central excitatory synapses. Like mammals, Drosophila utilizes auxiliary subunit(s) to modulate the formation and function of glutamatergic synapses. We have previously reported that Neto is an auxiliary protein essential for functional glutamate receptors and for organization of postsynaptic specializations. Here we report that synapse assembly and NMJ development are exquisitely sensitive to postsynaptic Neto levels. Furthermore, we show that Neto activity is controlled by Furin-type proteases, which regulate the processing and maturation of many developmentally important proteins, from growth factors and neuropeptides to extracellular matrix components. Such concerted control may serve to coordinate synapse assembly with synapse growth and developmental progression.
Vyšlo v časopise:
Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004988
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004988
Souhrn
Synapse development is initiated by genetic programs, but is coordinated by neuronal activity, by communication between the pre- and postsynaptic compartments, and by cellular signals that integrate the status of the whole organisms and its developmental progression. The molecular mechanisms underlining these processes are poorly understood. In particular, how neurotransmitter receptors are recruited and stabilized at central synapses remain the subject of intense research. The Drosophila NMJ is a glutamatergic synapse similar in composition and physiology with mammalian central excitatory synapses. Like mammals, Drosophila utilizes auxiliary subunit(s) to modulate the formation and function of glutamatergic synapses. We have previously reported that Neto is an auxiliary protein essential for functional glutamate receptors and for organization of postsynaptic specializations. Here we report that synapse assembly and NMJ development are exquisitely sensitive to postsynaptic Neto levels. Furthermore, we show that Neto activity is controlled by Furin-type proteases, which regulate the processing and maturation of many developmentally important proteins, from growth factors and neuropeptides to extracellular matrix components. Such concerted control may serve to coordinate synapse assembly with synapse growth and developmental progression.
Zdroje
1. Scannevin RH, Huganir RL (2000) Postsynaptic organization and regulation of excitatory synapses. Nat Rev Neurosci 1: 133–141. 11252776
2. Chen L, Tracy T, Nam CI (2007) Dynamics of postsynaptic glutamate receptor targeting. Curr Opin Neurobiol 17: 53–58. 17161597
3. Triller A, Choquet D (2005) Surface trafficking of receptors between synaptic and extrasynaptic membranes: and yet they do move! Trends Neurosci 28: 133–139. 15749166
4. Huganir RL, Nicoll RA (2013) AMPARs and synaptic plasticity: the last 25 years. Neuron 80: 704–717. doi: 10.1016/j.neuron.2013.10.025 24183021
5. Luscher C, Nicoll RA, Malenka RC, Muller D (2000) Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci 3: 545–550. 10816309
6. Wu H, Xiong WC, Mei L (2010) To build a synapse: signaling pathways in neuromuscular junction assembly. Development 137: 1017–1033. doi: 10.1242/dev.038711 20215342
7. Jin Y (2002) Synaptogenesis: insights from worm and fly. Curr Opin Neurobiol 12: 71–79. 11861167
8. Marques G (2005) Morphogens and synaptogenesis in Drosophila. J Neurobiol 64: 417–434. 16041756
9. Colon-Ramos DA (2009) Synapse formation in developing neural circuits. Curr Top Dev Biol 87: 53–79. doi: 10.1016/S0070-2153(09)01202-2 19427516
10. Thomas U, Sigrist SJ (2012) Glutamate receptors in synaptic assembly and plasticity: case studies on fly NMJs. Adv Exp Med Biol 970: 3–28. doi: 10.1007/978-3-7091-0932-8_1 22351049
11. DiAntonio A (2006) Glutamate receptors at the Drosophila neuromuscular junction. Int Rev Neurobiol 75: 165–179. 17137928
12. Marrus SB, Portman SL, Allen MJ, Moffat KG, DiAntonio A (2004) Differential localization of glutamate receptor subunits at the Drosophila neuromuscular junction. J Neurosci 24: 1406–1415. 14960613
13. Featherstone DE, Rushton E, Rohrbough J, Liebl F, Karr J, et al. (2005) An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromuscular junction. J Neurosci 25: 3199–3208. 15788777
14. Qin G, Schwarz T, Kittel RJ, Schmid A, Rasse TM, et al. (2005) Four different subunits are essential for expressing the synaptic glutamate receptor at neuromuscular junctions of Drosophila. J Neurosci 25: 3209–3218. 15788778
15. DiAntonio A, Petersen SA, Heckmann M, Goodman CS (1999) Glutamate receptor expression regulates quantal size and quantal content at the Drosophila neuromuscular junction. J Neurosci 19: 3023–3032. 10191319
16. Petersen SA, Fetter RD, Noordermeer JN, Goodman CS, DiAntonio A (1997) Genetic analysis of glutamate receptors in Drosophila reveals a retrograde signal regulating presynaptic transmitter release. Neuron 19: 1237–1248. 9427247
17. Schuster CM, Ultsch A, Schloss P, Cox JA, Schmitt B, et al. (1991) Molecular cloning of an invertebrate glutamate receptor subunit expressed in Drosophila muscle. Science 254: 112–114. 1681587
18. Broadie K, Bate M (1993) Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis. Nature 361: 350–353. 8426654
19. Broadie KS, Bate M (1993) Development of the embryonic neuromuscular synapse of Drosophila melanogaster. J Neurosci 13: 144–166. 8093713
20. Chen K, Featherstone DE (2005) Discs-large (DLG) is clustered by presynaptic innervation and regulates postsynaptic glutamate receptor subunit composition in Drosophila. BMC Biol 3: 1. 15638945
21. Sigrist SJ, Thiel PR, Reiff DF, Schuster CM (2002) The postsynaptic glutamate receptor subunit DGluR-IIA mediates long-term plasticity in Drosophila. J Neurosci 22: 7362–7372. 12196557
22. Rasse TM, Fouquet W, Schmid A, Kittel RJ, Mertel S, et al. (2005) Glutamate receptor dynamics organizing synapse formation in vivo. Nat Neurosci 8: 898–905. 16136672
23. Kim YJ, Bao H, Bonanno L, Zhang B, Serpe M (2012) Drosophila Neto is essential for clustering glutamate receptors at the neuromuscular junction. Genes Dev.
24. Ng D, Pitcher GM, Szilard RK, Sertie A, Kanisek M, et al. (2009) Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning. PLoS Biol 7: e41. doi: 10.1371/journal.pbio.1000041 19243221
25. Zhang W, St-Gelais F, Grabner CP, Trinidad JC, Sumioka A, et al. (2009) A transmembrane accessory subunit that modulates kainate-type glutamate receptors. Neuron 61: 385–396. doi: 10.1016/j.neuron.2008.12.014 19217376
26. Wang R, Mellem JE, Jensen M, Brockie PJ, Walker CS, et al. (2012) The SOL-2/Neto auxiliary protein modulates the function of AMPA-subtype ionotropic glutamate receptors. Neuron 75: 838–850. doi: 10.1016/j.neuron.2012.06.038 22958824
27. Copits BA, Robbins JS, Frausto S, Swanson GT (2011) Synaptic Targeting and Functional Modulation of GluK1 Kainate Receptors by the Auxiliary Neuropilin and Tolloid-Like (NETO) Proteins. J Neurosci 31: 7334–7340. doi: 10.1523/JNEUROSCI.0100-11.2011 21593317
28. Tang M, Pelkey KA, Ng D, Ivakine E, McBain CJ, et al. (2011) Neto1 Is an Auxiliary Subunit of Native Synaptic Kainate Receptors. J Neurosci 31: 10009–10018. doi: 10.1523/JNEUROSCI.6617-10.2011 21734292
29. Wyeth MS, Pelkey KA, Petralia RS, Salter MW, McInnes RR, et al. (2014) Neto auxiliary protein interactions regulate kainate and NMDA receptor subunit localization at mossy fiber-CA3 pyramidal cell synapses. J Neurosci 34: 622–628. doi: 10.1523/JNEUROSCI.3098-13.2014 24403160
30. Schmid A, Qin G, Wichmann C, Kittel RJ, Mertel S, et al. (2006) Non-NMDA-type glutamate receptors are essential for maturation but not for initial assembly of synapses at Drosophila neuromuscular junctions. J Neurosci 26: 11267–11277. 17079654
31. Guan B, Hartmann B, Kho YH, Gorczyca M, Budnik V (1996) The Drosophila tumor suppressor gene, dlg, is involved in structural plasticity at a glutamatergic synapse. Curr Biol 6: 695–706. 8793296
32. Marques G, Zhang B (2006) Retrograde signaling that regulates synaptic development and function at the Drosophila neuromuscular junction. Int Rev Neurobiol 75: 267–285. 17137932
33. Sulkowski M, Kim YJ, Serpe M (2014) Postsynaptic glutamate receptors regulate local BMP signaling at the Drosophila neuromuscular junction. Development 141: 436–447. doi: 10.1242/dev.097758 24353060
34. Massague J (1990) The transforming growth factor-beta family. Annu Rev Cell Biol 6: 597–641. 2177343
35. Degnin C, Jean F, Thomas G, Christian JL (2004) Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4. Mol Biol Cell 15: 5012–5020. 15356272
36. Kunnapuu J, Bjorkgren I, Shimmi O (2009) The Drosophila DPP signal is produced by cleavage of its proprotein at evolutionary diversified furin-recognition sites. Proc Natl Acad Sci U S A 106: 8501–8506. doi: 10.1073/pnas.0809885106 19433798
37. Akiyama T, Marques G, Wharton KA (2012) A large bioactive BMP ligand with distinct signaling properties is produced by alternative proconvertase processing. Sci Signal 5: ra28. doi: 10.1126/scisignal.2002549 22472650
38. Wharton KA, Serpe M (2013) Fine-tuned shuttles for bone morphogenetic proteins. Curr Opin Genet Dev.
39. Ellis JE, Parker L, Cho J, Arora K (2010) Activin signaling functions upstream of Gbb to regulate synaptic growth at the Drosophila neuromuscular junction. Dev Biol 342: 121–133. doi: 10.1016/j.ydbio.2010.03.012 20346940
40. Fuentes-Medel Y, Ashley J, Barria R, Maloney R, Freeman M, et al. (2012) Integration of a Retrograde Signal during Synapse Formation by Glia-Secreted TGF-beta Ligand. Curr Biol 22: 1831–1838. doi: 10.1016/j.cub.2012.07.063 22959350
41. Wagh DA, Rasse TM, Asan E, Hofbauer A, Schwenkert I, et al. (2006) Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. Neuron 49: 833–844. 16543132
42. Higashi-Kovtun ME, Mosca TJ, Dickman DK, Meinertzhagen IA, Schwarz TL (2010) Importin-beta11 regulates synaptic phosphorylated mothers against decapentaplegic, and thereby influences synaptic development and function at the Drosophila neuromuscular junction. J Neurosci 30: 5253–5268. doi: 10.1523/JNEUROSCI.3739-09.2010 20392948
43. Zinsmaier KE, Eberle KK, Buchner E, Walter N, Benzer S (1994) Paralysis and early death in cysteine string protein mutants of Drosophila. Science 263: 977–980. 8310297
44. McMahan UJ (1990) The agrin hypothesis. Cold Spring Harb Symp Quant Biol 55: 407–418. 1966767
45. O'Brien RJ, Xu D, Petralia RS, Steward O, Huganir RL, et al. (1999) Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23: 309–323. 10399937
46. Shepherd JD, Huganir RL (2007) The cell biology of synaptic plasticity: AMPA receptor trafficking. Annu Rev Cell Dev Biol 23: 613–643. 17506699
47. Nakayama K (1997) Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins. Biochem J 327 (Pt 3): 625–635.
48. Roebroek AJ, Creemers JW, Pauli IG, Bogaert T, Van de Ven WJ (1993) Generation of structural and functional diversity in furin-like proteins in Drosophila melanogaster by alternative splicing of the Dfur1 gene. EMBO J 12: 1853–1870. 8491178
49. Roebroek AJ, Ayoubi TA, Creemers JW, Pauli IG, Van de Ven WJ (1995) The Dfur2 gene of Drosophila melanogaster: genetic organization, expression during embryogenesis, and pro-protein processing activity of its translational product Dfurin2. DNA Cell Biol 14: 223–234. 7880443
50. Siekhaus DE, Fuller RS (1999) A role for amontillado, the Drosophila homolog of the neuropeptide precursor processing protease PC2, in triggering hatching behavior. J Neurosci 19: 6942–6954. 10436051
51. Rayburn LY, Gooding HC, Choksi SP, Maloney D, Kidd AR 3rd, et al. (2003) amontillado, the Drosophila homolog of the prohormone processing protease PC2, is required during embryogenesis and early larval development. Genetics 163: 227–237. 12586710
52. Hayflick JS, Wolfgang WJ, Forte MA, Thomas G (1992) A unique Kex2-like endoprotease from Drosophila melanogaster is expressed in the central nervous system during early embryogenesis. J Neurosci 12: 705–717. 1545235
53. Seidah NG, Prat A (2012) The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov 11: 367–383. 22679642
54. Sone M, Suzuki E, Hoshino M, Hou D, Kuromi H, et al. (2000) Synaptic development is controlled in the periactive zones of Drosophila synapses. Development 127: 4157–4168. 10976048
55. Kim YJ, Serpe M (2013) Building a synapse: A complex matter. Fly (Austin) 7.
56. Broadie K, Bate M (1993) Muscle development is independent of innervation during Drosophila embryogenesis. Development 119: 533–543. 8287801
57. Rohrbough J, Rushton E, Woodruff E 3rd, Fergestad T, Vigneswaran K, et al. (2007) Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation. Genes Dev 21: 2607–2628. 17901219
58. Sengle G, Ono RN, Sasaki T, Sakai LY (2011) Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: extracellular matrix interactions and growth factor bioavailability. J Biol Chem 286: 5087–5099. doi: 10.1074/jbc.M110.188615 21135108
59. Dejima K, Kanai MI, Akiyama T, Levings DC, Nakato H (2011) Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans. J Biol Chem 286: 17103–17111. doi: 10.1074/jbc.M110.208082 21454551
60. Mac Sweeney A, Gil-Parrado S, Vinzenz D, Bernardi A, Hein A, et al. (2008) Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases. J Mol Biol 384: 228–239. doi: 10.1016/j.jmb.2008.09.029 18824173
61. Koon AC, Ashley J, Barria R, DasGupta S, Brain R, et al. (2011) Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling. Nat Neurosci 14: 190–199. doi: 10.1038/nn.2716 21186359
62. Seidah NG, Mayer G, Zaid A, Rousselet E, Nassoury N, et al. (2008) The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol 40: 1111–1125. doi: 10.1016/j.biocel.2008.01.030 18343183
63. Karr J, Vagin V, Chen K, Ganesan S, Olenkina O, et al. (2009) Regulation of glutamate receptor subunit availability by microRNAs. J Cell Biol 185: 685–697. doi: 10.1083/jcb.200902062 19433455
64. Serpe M, Umulis D, Ralston A, Chen J, Olson DJ, et al. (2008) The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila. Dev Cell 14: 940–953. doi: 10.1016/j.devcel.2008.03.023 18539121
65. Stewart BA, Atwood HL, Renger JJ, Wang J, Wu CF (1994) Improved stability of Drosophila larval neuromuscular preparations in haemolymph-like physiological solutions. J Comp Physiol A 175: 179–191. 8071894
66. Budnik V, Gorczyca M, Prokop A (2006) Selected methods for the anatomical study of Drosophila embryonic and larval neuromuscular junctions. Int Rev Neurobiol 75: 323–365. 17137935
67. Liebl FL, Chen K, Karr J, Sheng Q, Featherstone DE (2005) Increased synaptic microtubules and altered synapse development in Drosophila sec8 mutants. BMC Biol 3: 27. 16351720
68. Conder R, Yu H, Ricos M, Hing H, Chia W, et al. (2004) dPak is required for integrity of the leading edge cytoskeleton during Drosophila dorsal closure but does not signal through the JNK cascade. Dev Biol 276: 378–390. 15581872
69. Serpe M, Ralston A, Blair SS, O'Connor MB (2005) Matching catalytic activity to developmental function: tolloid-related processes Sog in order to help specify the posterior crossvein in the Drosophila wing. Development 132: 2645–2656. 15872004
70. Ramachandran P, Budnik V (2010) Electron microscopy of Drosophila larval neuromuscular junctions. Cold Spring Harb Protoc 2010: pdb prot5474.
71. Bao H, Daniels RW, MacLeod GT, Charlton MP, Atwood HL, et al. (2005) AP180 maintains the distribution of synaptic and vesicle proteins in the nerve terminal and indirectly regulates the efficacy of Ca2+-triggered exocytosis. J Neurophysiol 94: 1888–1903. 15888532
72. Zhang B, Koh YH, Beckstead RB, Budnik V, Ganetzky B, et al. (1998) Synaptic vesicle size and number are regulated by a clathrin adaptor protein required for endocytosis. Neuron 21: 1465–1475. 9883738
73. Ide D (2013) Electrophysiology tool construction. Curr Protoc Neurosci Chapter 6: Unit 6 26.
74. Gho M (1994) Voltage-clamp analysis of gap junctions between embryonic muscles in Drosophila. J Physiol 481 (Pt 2): 371–383. 7537815
75. Feeney CJ, Karunanithi S, Pearce J, Govind CK, Atwood HL (1998) Motor nerve terminals on abdominal muscles in larval flesh flies, Sarcophaga bullata: comparisons with Drosophila. J Comp Neurol 402: 197–209. 9845243
76. Stevens CF (1976) A comment on Martin's relation. Biophys J 16: 891–895. 938729
77. Lagow RD, Bao H, Cohen EN, Daniels RW, Zuzek A, et al. (2007) Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion. PLoS Biol 5: e72. 17341138
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2015 Číslo 2
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Genomic Selection and Association Mapping in Rice (): Effect of Trait Genetic Architecture, Training Population Composition, Marker Number and Statistical Model on Accuracy of Rice Genomic Selection in Elite, Tropical Rice Breeding Lines
- Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling
- Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks
- Proteotoxic Stress Induces Phosphorylation of p62/SQSTM1 by ULK1 to Regulate Selective Autophagic Clearance of Protein Aggregates