Participation of Ca2+-acceptor proteins in the mechanisms of the exo-endocytic cycle of synaptic vesicles in the motor nerve endings of the somatic musculature of the earthworm Lumbricus terrestris

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Abstract

Using fluorescence microscopy, we studied the participation of Ca2+-acceptor proteins in the processes of the exo-endocytotic cycle of neurotransmitter quantal secretion in the neuromuscular junction of the somatic muscle of the earthworm Lumbricus terrestris. Inhibition of calcineurin, calmodulin and Ca2+/calmodulin dependent protein kinases led to an increase in the process of endocytosis. Blocking the phosphorylation of synaptic proteins enhances the process of endocytosis, causes an increase in the size of the total vesicular pool and accelerates the turnover of synaptic vesicles. It can be concluded that calcium modulation of vesicle exo-endocytosis at the synapses of the evolutionarily primary somatic muscles of annelids occurs with the participation of calcineurin, calmodulin and Ca2+/calmodulin-dependent protein kinases.

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About the authors

L. F. Nurullin

Federal Research Center “Kazan Scientific Center of Russian Academy of Sciences”; Kazan State Medical University

Author for correspondence.
Email: lenizn@yandex.ru

Kazan Institute of Biochemistry and Biophysics

Russian Federation, Kazan; Kazan

N. D. Almazov

Kazan State Medical University

Email: lenizn@yandex.ru
Russian Federation, Kazan

E. M. Volkov

Kazan State Medical University

Email: euroworm@mail.ru
Russian Federation, Kazan

References

  1. Wu LG, Hamid E, Shin W, Chiang HC (2014) Exocytosis and endocytosis: modes, functions, and coupling mechanisms. Annu Rev Physiol 76: 301–331. https://doi.org/10.1146/annurev-physiol-021113-170305
  2. Betz WJ, Wu LG (1995) Synaptic transmission. Kinetics of synaptic-vesicle recycling. Curr Biol 5: 1098–1101. https://doi.org/10.1016/s0960-9822(95)00220-x
  3. Rizzoli SO, Betz WJ (2005) Synaptic vesicle pools. Nat Rev Neurosci 6: 57–69. https://doi.org/10.1038/nrn1583
  4. Sudhof TC (2004) The synaptic vesicle cycle. Annu Rev Neurosci 27: 509–547. https://doi.org/10.1146/annurev.neuro.26.041002.131412
  5. Igarashi M, Watanabe M (2007) Roles of calmodulin and calmodulin-binding proteins in synaptic vesicle recycling during regulated exocytosis at submicromolar Ca2+ concentrations. Neurosci Res 58: 226–233. https://doi.org/10.1016/j.neures.2007.03.005
  6. Volkov EM, Nurullin LF, Nikolsky EE, Švandová I, Vyskočil F (2000) Participation of electrogenic Na+-K+-ATPase in the membrane potential of earthworm body wall muscles. Physiol Res 49: 481–484. http://www.biomed.cas.cz/physiolres/pdf/49/49_481.pdf
  7. He LS, Rue MCP, Morozova EO, Powell DJ, James EJ, Kar M, Marder E (2020) Rapid adaptation to elevated extracellular potassium in the pyloric circuit of the crab, Cancer borealis. J Neurophysiol 123: 2075–2089. https://doi.org/10.1152/jn.00135.2020
  8. Williams CL, Smith SM (2018) Calcium dependence of spontaneous neurotransmitter release. J Neurosci Res 96: 335–347. https://doi.org/10.1002/jnr.24116
  9. Creamer TP (2020) Calcineurin. Cell Commun Signal 18: 137. https://doi.org/10.1186/s12964-020-00636-4
  10. Kumashiro S, Lu YF, Tomizawa K, Matsushita M, Wei FY, Matsui H (2005) Regulation of synaptic vesicle recycling by calcineurin in different vesicle pools. Neurosci Res 51: 435–443. https://doi.org/10.1016/j.neures.2004.12.018
  11. Kuromi H, Kidokoro Y (1999) The optically determined size of exo/endo cycling vesicle pool correlates with the quantal content at the neuromuscular junction of Drosophila larvae. J Neurosci 19: 1557–1565. https://doi.org/10.1523/jneurosci.19-05-01557.1999
  12. Tokumitsu H, Sakagami H (2022) Molecular Mechanisms Underlying Ca2+/Calmodulin-Dependent Protein Kinase Kinase Signal Transduction. Int J Mol Sci 23: 11025. https://doi.org/10.3390/ijms231911025
  13. Kennedy G, Gibson O, T O'Hare D, Mills IG, Evergren E (2023) The role of CaMKK2 in Golgi-associated vesicle trafficking. Biochem Soc Trans 51: 331–342. https://doi.org/10.1042/bst20220833
  14. Tokumitsu H, Inuzuka H, Ishikawa Y, Ikeda M, Saji I, Kobayashi R (2002) STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. J Biol Chem 277: 15813–15818. https://doi.org/10.1074/jbc.M201075200
  15. Mao LM, Jin DZ, Xue B, Chu XP, Wang JQ (2014) Phosphorylation and regulation of glutamate receptors by CaMKII. Sheng Li Xue Bao 66: 365–372. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4435801/
  16. Wang ZW (2008) Regulation of synaptic transmission by presynaptic CaMKII and BK channels. Mol Neurobiol 38: 153–166. https://doi.org/10.1007/s12035-008-8039-7
  17. Wu XS, McNeil BD, Xu J, Fan J, Xue L, Melicoff E, Adachi R, Bai L, Wu LG (2009) Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal. Nat Neurosci 12: 1003–1010. https://doi.org/10.1038/nn.2355
  18. Randic M, Padjen A (1967) Effect of calcium ions on the release of acetylcholine from the cerebral cortex. Nature 215: 990. https://doi.org/10.1038/215990a0
  19. Simpson LL (1968) The role of calcium in neurohumoral and neurohormonal extrusion processes. J Pharm Pharmacol 20: 889–910. https://doi.org/10.1111/j.2042-7158.1968.tb09672.x
  20. Tan TC, Valova VA, Malladi CS, Graham ME, Berven LA, Jupp OJ, Hansra G, McClure SJ, Sarcevic B, Boadle RA, Larsen MR, Cousin MA, Robinson PJ (2003) Cdk5 is essential for synaptic vesicle endocytosis. Nat Cell Biol 5: 701–710. https://doi.org/10.1038/ncb1020
  21. Cousin MA, Tan TC, Robinson PJ (2001) Protein phosphorylation is required for endocytosis in nerve terminals: potential role for the dephosphins dynamin I and synaptojanin, but not AP180 or amphiphysin. J Neurochem 76: 105–116. https://doi.org/10.1046/j.1471-4159.2001.00049.x
  22. Marra V, Burden JJ, Thorpe JR, Smith IT, Smith SL, Häusser M, Branco T, Staras K (2012) A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses. Neuron 76: 579–589. https://doi.org/10.1016/j.neuron.2012.08.042
  23. Kuromi H, Yoshihara M, Kidokoro Y (1997) An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae. Neurosci Res 27: 101–113. https://doi.org/10.1016/s0168-0102(96)01132-7
  24. Igarashi M, Watanabe M (2007) Roles of calmodulin and calmodulin-binding proteins in synaptic vesicle recycling during regulated exocytosis at submicromolar Ca2+ concentrations. Neurosci Res 58: 226–233. https://doi.org/10.1016/j.neures.2007.03.005
  25. Sakaba T, Neher E (2001) Calmodulin mediates rapid recruitment of fast-releasing synaptic vesicles at a calyx-type synapse. Neuron 32: 1119–1131. https://doi.org/10.1016/s0896-6273(01)00543-8
  26. Xue R, Meng H, Yin J, Xia J, Hu Z, Liu H (2021) The Role of Calmodulin vs. Synaptotagmin in Exocytosis. Front Mol Neurosci 14: 691363. https://doi.org/10.3389/fnmol.2021.691363
  27. Wang ZW (2008) Regulation of synaptic transmission by presynaptic CaMKII and BK channels. Mol Neurobiol. 38: 153–166. https://doi.org/10.1007/s12035-008-8039-7

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2. Fig. 1. Fluorescence of neuromuscular synapses of earthworm somatic muscle cells loaded with the lipophilic dye FM2–10. (a) – 0 min, (b) – after 5 min of dye “unloading” at 40 mM K+ in the surrounding solution. Scale bar: 20 µm.

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3. Fig. 2. Effect of DMSO, absence of Ca2+ ions in solution, calcineurin inhibitor – cyclosporin A, Ca2+/calmodulin-dependent protein kinase kinase inhibitor – STO-609, calmodulin antagonist – W-5 hydrochloride on the fluorescence value of motor nerve terminals of the earthworm somatic muscle cell preparation loaded with lipophilic dye FM2–10. a. u. – relative units.

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4. Fig. 3. Effect of calcineurin inhibitor – cyclosporin A, Ca2+/calmodulin-dependent protein kinase kinase inhibitor – STO-609, calmodulin antagonist – W-5 hydrochloride, absence of Ca2+ ions in the surrounding solution (0 mM Ca2+), calcium chelator BAPTA-AM on the “unloading” of motor nerve terminals of the earthworm somatic muscle cell preparation stained with the fluorescent dye FM2–10. In a separate series of experiments, the fading of the FM2–10 dye in a normal solution (4 mM K+) was monitored for 5 min.

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