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The Role of Cholesterol in the Exo- and Endocytosis of Synaptic Vesicles in Frog Motor Nerve Endings

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Experiments on frog neuromuscular preparations using electrophysiological (two-electrode voltage clamping) and optical (with the fluorescent endocytic stain FM1-43) methods were performed to study the importance of membrane cholesterol in the exo- and endocytic cycle of synaptic vesicles (SV) in motor nerve endings in conditions of prolonged rhythmic stimulation of the motor nerve (20 impulses/sec, 3 min). Extraction of cholesterol from the superficial plasma membranes using methyl-β-cyclodextrin (1 mM) led to marked changes in SV recycling. There was weakening of SV exocytosis and suppression of processes leading to the recovery of SV populations with rapid readiness to release neurotransmitter. When cholesterol was leached from the outer membranes and the membranes of SV undergoing recycling, these effects were supplemented by impairments to SV endocytosis and recycling. Thus, plasma membrane cholesterol plays a key role in the processes of exocytosis, while the efficiency of endocytosis depends on cholesterol in SV membranes.

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References

  1. A. L. Zefirov, “The vesicular cycle in presynaptic nerve terminals,” Ros. Fiziol. Zh. im. I. M. Sechenova, 93, No. 5, 554–563 (2007).

    Google Scholar 

  2. A. L. Zefirov, P. N. Grigoriev, A. M. Petrov, M. G. Minlebaev, and G. F. Sitdikova, “In vivo fluorescence studies of motor nerve endings in frogs using the endocytic marker FM1-43,” Tsitologiya, 45, No. 12, 1163–1171 (2003).

    CAS  Google Scholar 

  3. A. L. Zefirov, A. V. Zakharov, R. D. Mukhamotzyanov, and A. M. Petrov, “Characteristics of the circulation of synaptic vesicles in motor nerve endings in frogs and mice,” Zh. Evolyuts. Biokhim. Fiziol., 44, No. 6, 603–612 (2008).

    CAS  Google Scholar 

  4. A. L. Zefirov, A. V. Zakharov, R. D. Mukhamotzyanov, A. M. Petrov, and G. F. Sitdikova, “The vesicular cycle in motor nerve endings in the mouse diaphragm,” Ros. Fiziol. Zh. im. I. M. Sechenova, 94, No. 2, 129–141 (2008).

    CAS  Google Scholar 

  5. A. M. Petrov, A. R. Giniatullin, and A. L. Zefirov, “The role of the cAMP signal cascade in the circulation of synaptic vesicles in motor nerve endings in frogs,” Neirokhimiya, 25, No. 3, 202–210 (2008).

    CAS  Google Scholar 

  6. W. J. Betz and G. S. Bewick, “Optical monitoring of transmitter release and synaptic vesicle recycling at the frog neuromuscular junction,” J. Physiol. (London), 460, 287–309 (1993).

    CAS  Google Scholar 

  7. A. E. Christian, M. P. Haynes, M. C. Phillips, and G. H. Rothblat, “Use of cyclodextrins for manipulating cellular cholesterol content,” J. Lipid Res., 38, 2264–2272 (1997).

    CAS  PubMed  Google Scholar 

  8. F. Di Paolo and P. De Cailli, “Phosphoinositides in cell regulation and membrane dynamics,” Nature, 443, 651–657 (2006).

    Article  PubMed  Google Scholar 

  9. C. Gil, A. Soler-Jover, J. Blasi, and J. Aguilera, “Synaptic proteins and SNARE complexes are localized in lipid rafts from rat brain synaptosomes,” Biochem. Biophys. Res. Commun., 329, 117–124 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. A. Giniatullin, F. Darios, A. Shakirzyanova, B. Davletov, and R. Giniatullin, “SNAP25 is a pre-synaptic target for the depressant action of reactive oxygen species on transmitter release,” J. Neurochem., 98, 1789–1797 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. A. R. Giniatullin, S. N. Grishin, E. R. Sharifullina, A. M. Petrov, A. M. Zefirov, and R. A. Giniatullin, “Reactive oxygen species contribute to the presynaptic action of extracellular ATP at the frog neuromuscular junction,” J. Physiol., 565, No. 1, 229–242 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. M. I. Glavinovic, “Voltage clamping of unparalysed cut rat diaphragm for study of transmitter release,” J. Physiol., 290, 467–480 (1979).

    CAS  PubMed  Google Scholar 

  13. B. Granseth, B. Odermatt, S. Royle, and J. Lagnado, “Clathrin-mediated endocytosis: the physiological mechanism of vesicle retrieval at hippocampal synapses,” J. Physiol., 585, No. 3, 681–686 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. J. E. Heuser, T. S. Reese, M. J. Dennis, and L. Jan, “Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release,” J. Cell Biol., 81, 275–300 (1979).

    Article  CAS  PubMed  Google Scholar 

  15. J.-Y. Jia, S. Lamer, M. Schuemann, M. R. Schmidt, E. Krause, and V. Haucke, “Quantitative proteomic analysis of detergent-resistant membranes from chemical synapses: Evidence for cholesterol as spatial organizer of synaptic vesicle cycling,” Mol. Cell Proteomics, 5, 2060–2071 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. N. Jung and V. Haucke, “Clathrin-mediated endocytosis at synapses,” Traffic, 8, 1129–1136 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. T. Lang, “SNARE proteins and ‘membrane rafts’,” J. Physiol., 585, No. 3, 693–698 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. A. M. Petrov, A. R. Giniatullin, G. F. Sitdikova, and A. L. Zefirov, “The role of cGMP-dependent signaling pathway in synaptic vesicle cycle at the frog motor nerve terminals,” J. Neurosci., 28, No. 49, 13216–13222 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. F. W. Pfrieger, “Role of cholesterol in synapse formation and function,” Biochem. Biophys. Acta, 1610, 271–280 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. J. Rohrbough and K. Broadie, “Lipid regulation of the synaptic vesicle cycle,” Nature Rev. Neurosci., 6, 139–150 (2005).

    Article  CAS  Google Scholar 

  21. J. Rohrbough, E. Rushton, L. Palanker, E. Woodruff, H. J. G. Matthies, U. Acharya, K. J. Acharya, and K. Broadie, “Ceramidase regulates synaptic vesicle exocytosis and trafficking,” J. Neurosci., 24, No. 36, 7789–7803 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. T. C. Sudhof, “The synaptic vesicle cycle,” Ann. Rev. Neurosci., 27, 509–547 (2004).

    Article  PubMed  Google Scholar 

  23. E. Taverna, E. Saba, J. Rowe, M. Francolini, F. Clementi, and P. Rosa, “Role of lipid micro-domains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes,” J. Biol. Chem., 279, 5127–5134 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. H. Weixing, L. Hewang,V. M. Van Anthony, P. M. Annabelle, D. I. Mustafa, Q. Xiaoyang, N. Aruna, Q. T. Mark, F. A. Robin, J. A. Pedro, and Y. Peiying, “Lipid Rafts Keep NADPH oxidase in the inactive state in human renal proximal tubule cells,” Hypertension, 51, No. 2, 481–487 (2008).

    Article  Google Scholar 

  25. O. Zamir and M. P. Charlton, “Cholesterol and synaptic transmitter release at crayfish neuromuscular junction,” J. Physiol., 571, No. 1, 83–99 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. A. L. Zefirov, M. M. Abdrakhmanov, M. A. Mukhamedyarov, and P. N. Grigoryev, “ The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at the frog motor nerve terminals,” Neuroscience, 143, 905–910 (2006).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Kazan State Medical University, 49 Butlerov Street, 420012, Kazan, Russia

    A. M. Petrov, M. R. Kasimov, A. R. Giniatullin, O. I. Tarakanova & A. L. Zefirov

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  1. A. M. Petrov
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  2. M. R. Kasimov
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  3. A. R. Giniatullin
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  4. O. I. Tarakanova
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  5. A. L. Zefirov
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Correspondence to A. M. Petrov.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 95, No. 7, pp. 762–772, July, 2009.

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Petrov, A.M., Kasimov, M.R., Giniatullin, A.R. et al. The Role of Cholesterol in the Exo- and Endocytosis of Synaptic Vesicles in Frog Motor Nerve Endings. Neurosci Behav Physi 40, 894–901 (2010). https://doi.org/10.1007/s11055-010-9338-9

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  • DOI: https://doi.org/10.1007/s11055-010-9338-9

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