Malfunctions in synaptic membrane trafficking in early pathology of Parkinson’s disease: new molecular clues

Elena Sopova; Olga Korenkova; Oleg Shupliakov

doi:10.21638/11701/spbu03.2017.406

Authors

Elena Sopova Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7–9, Saint Petersburg, 199034, Russian Federation
Olga Korenkova Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7–9, Saint Petersburg, 199034, Russian Federation
Oleg Shupliakov Department of Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya nab., 7–9, Saint Petersburg, 199034, Russian Federation https://orcid.org/0000-0001-5352-6848

DOI:

https://doi.org/10.21638/11701/spbu03.2017.406

Abstract

The midbrain dopaminergic neurons of the substantia nigra and the ventral tegmental area play vital roles in the regulation of voluntary movement, emotion and reward in humans. These neurons are highly metabolic and are under constant oxidative stress. The dopaminergic neurons form extensive synaptic projections to the striatum. When these neurons start dying or when their synaptic connections fail, humans develop Parkinson's disease. This disease is accompanied by the accumulation of toxic α-synuclein-containing protein aggregates in nigrostriatal processes. Synucleins accumulate in a majority of healthy nerve terminals in the central nervous system, but what causes the formation of pathological synuclein aggregates is unclear. Recent studies point out that the interface between membrane trafficking in the nerve terminal and the autophagy–lysosomal pathway is the site for the aggregate assembly. An urgent goal is to find therapeutic targets at early stages of the disease when neurons are still functional.

Keywords:

synapse, synaptic proteins, atophagy-lysosomal pathway, developmental transcription factors, Parkinson's disease

Downloads

Download data is not yet available.

References

Bartels, T., Choi, J. G. and Selkoe, D. J. 2011. Alpha-synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477(7362):107−110. https://doi.org/10.1038/nature10324

Boassa, D., Berlanga, M. L., Yang, M. A., Terada, M., Hu, J., Bushong, E. A., Hwang, M., Masliah, E., George, J. M. and Ellisman, M. H. 2013. Mapping the subcellular distribution of alpha-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: Implications for parkinson’s disease pathogenesis. Journal of Neuroscience 33(6):2605−2615. https://doi.org/10.1523/JNEUROSCI.2898-12.2013

Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N. and Braak, E. 2003. Staging of brain pathology related to sporadic parkinson’s disease. Neurobiology of Aging 24(2):197−211. https://doi.org/10.1016/S0197-4580(02)00065-9

Burre, J., Sharma, M. and Sudhof, T. C. 2012. Systematic mutagenesis of alpha-synuclein reveals distinct sequence requirements for physiological and pathological activities. Journal of Neuroscience 32(43):15227−15242. https://doi.org/10.1523/JNEUROSCI.3545-12.2012

Burre, J., Vivona, S., Diao, J., Sharma, M., Brunger, A. T. and Sudhof, T. C. 2013. Properties of native brain alphasynuclein. Nature 498(7453):E4−E6; discussion E6-7. https://doi.org/10.1038/nature12125

Cao, M., Milosevic, I., Giovedi, S. and De Camilli, P. 2014. Upregulation of parkin in endophilin mutant mice. Journal of Neuroscience 34(49):16544−16549. https://doi.org/10.1523/JNEUROSCI.1710-14.2014

Cao, M., Wu, Y., Ashrafi, G., McCartney, A. J., Wheeler, H., Bushong, E. A., Boassa, D., Ellisman, M. H., Ryan, T. A. and De Camilli, P. 2017. Parkinson sac domain mutation in synaptojanin 1 impairs clathrin uncoating at synapses and triggers dystrophic changes in dopaminergic axons. Neuron 93(4):882−896 e885. https://doi.org/10.1016/j.neuron.2017.01.019

Chai, Y. J., Sierecki, E., Tomatis, V. M., Gormal, R. S., Giles, N., Morrow, I. C., Xia, D., Gotz, J., Parton, R. G., Collins, B. M., Gambin, Y. and Meunier, F. A. 2016. Munc18-1 is a molecular chaperone for alpha-synuclein, controlling its self-replicating aggregation. Journal of Cell Biology 214(6):705−718. https://doi.org/10.1083/jcb.201512016

Chung, K. K., Zhang, Y., Lim, K. L., Tanaka, Y., Huang, H., Gao, J., Ross, C. A., Dawson, V. L. and Dawson, T. M. 2001. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: Implications for lewy-body formation in parkinson disease. Nature Medicine 7(10):1144−1150. https://doi.org/10.1038/nm1001-1144

Cookson, M. R. and Bandmann, O. 2010. Parkinson’s disease: Insights from pathways. Human Molecular Genetics 19(R1):R21−R27. https://doi.org/10.1093/hmg/ddq167

Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T. and Sulzer, D. 2004. Impaired degradation of mutant alphasynuclein by chaperone-mediated autophagy. Science 305(5688):1292−1295. https://doi.org/10.1126/science.1101738

Engelender, S. 2008. Ubiquitination of alpha-synuclein and autophagy in parkinson’s disease. Autophagy 4(3):372−374. https://doi.org/10.4161/auto.5604

Esposito, G., Ana Clara, F. and Verstreken, P. 2012. Synaptic vesicle trafficking and parkinson’s disease. Developmental Neurobiology 72(1):134−144. https://doi.org/10.1002/dneu.20916

Gad, H., Ringstad, N., Low, P., Kjaerulff, O., Gustafsson, J., Wenk, M., Di Paolo, G., Nemoto, Y., Crun, J., Ellisman, M. H., De Camilli, P., Shupliakov, O. and Brodin, L. 2000. Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the sh3 domain of endophilin. Neuron 27(2):301−312. https://doi.org/10.1016/S0896-6273(00)00038-6

Guzman, J. N., Sanchez-Padilla, J., Wokosin, D., Kondapalli, J., Ilijic, E., Schumacker, P. T. and Surmeier, D. J. 2010. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by dj-1. Nature 468(7324):696−700. https://doi.org/10.1038/nature09536

Hansen, C. and Li, J. Y. 2012. Beyond alpha-synuclein transfer: Pathology propagation in parkinson’s disease. Trends in Molecular Medicine 18(5):248−255. https://doi.org/10.1016/j.molmed.2012.03.002

Heutink, P. and Verhage, M. 2012. Neurodegeneration: New road leads back to the synapse. Neuron 75(6):935−938. https://doi.org/10.1016/j.neuron.2012.09.006

Krabben, L., Fassio, A., Bhatia, V. K., Pechstein, A., Onofri, F., Fadda, M., Messa, M., Rao, Y., Shupliakov, O., Stamou, D., Benfenati, F. and Haucke, V. 2011. Synapsin i senses membrane curvature by an amphipathic lipid packing sensor motif. Journal of Neuroscience 31(49):18149−18154. https://doi.org/10.1523/JNEUROSCI.4345-11.2011

Laguna, A., Schintu, N., Nobre, A., Alvarsson, A., Volakakis, N., Jacobsen, J. K., Gomez-Galan, M., Sopova, E., Joodmardi, E., Yoshitake, T., Deng, Q., Kehr, J., Ericson, J., Svenningsson, P., Shupliakov, O. and Perlmann, T. 2015. Dopaminergic control of autophagic-lysosomal function implicates lmx1b in parkinson’s disease. Nature Neuroscience 18(6):826−835. https://doi.org/10.1038/nn.4004

Lotharius, J. and Brundin, P. 2002. Pathogenesis of parkinson’s disease: Dopamine, vesicles and alpha-synuclein. Nature Reviews Neuroscience 3(12):932−942. https://doi.org/10.1038/nrn983

Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q. and Lee, V. M. 2012. Pathological alpha-synuclein transmission initiates parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109):949−953. https://doi.org/10.1126/science.1227157

Mandler, M., Valera, E., Rockenstein, E., Weninger, H., Patrick, C., Adame, A., Santic, R., Meindl, S., Vigl, B., Smrzka, O., Schneeberger, A., Mattner, F. and Masliah, E. 2014. Nextgeneration active immunization approach for synucleinopathies: Implications for parkinson’s disease clinical trials. Acta Neuropathologica 127(6):861−879. https://doi.org/10.1007/s00401-014-1256-4

Maroteaux, L., Campanelli, J. T. and Scheller, R. H. 1988. Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. Journal of Neuroscience 8(8):2804−2815. https://doi.org/10.1523/JNEUROSCI.08-08-02804.1988

Matta, S., Van Kolen, K., da Cunha, R., van den Bogaart, G., Mandemakers, W., Miskiewicz, K., De Bock, P. J., Morais, V. A., Vilain, S., Haddad, D., Delbroek, L., Swerts, J., Chavez-Gutierrez, L., Esposito, G., Daneels, G., Karran, E., Holt, M., Gevaert, K., Moechars, D. W., De Strooper, B. and Verstreken, P. 2012. Lrrk2 controls an endoa phosphorylation cycle in synaptic endocytosis. Neuron 75(6):1008−1021. https://doi.org/10.1016/j.neuron.2012.08.022

Milosevic, I., Giovedi, S., Lou, X., Raimondi, A., Collesi, C., Shen, H., Paradise, S., O’Toole, E., Ferguson, S., Cremona, O. and De Camilli, P. 2011. Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron 72(4):587−601. https://doi.org/10.1016/j.neuron.2011.08.029

Moors, T. E., Hoozemans, J. J., Ingrassia, A., Beccari, T., Parnetti, L., Chartier-Harlin, M. C. and van de Berg, W. D. 2017. Therapeutic potential of autophagy-enhancing agents in parkinson’s disease. Molecular Neurodegeneration 12(1):11. https://doi.org/10.1186/s13024-017-0154-3

Murdoch, J. D., Rostosky, C. M., Gowrisankaran, S., Arora, A. S., Soukup, S. F., Vidal, R., Capece, V., Freytag, S., Fischer, A., Verstreken, P., Bonn, S., Raimundo, N. and Milosevic, I. 2016. Endophilin-a deficiency induces the foxo3afbxo32 network in the brain and causes dysregulation of autophagy and the ubiquitin-proteasome system. Cell Reports 17(4):1071−1086. https://doi.org/10.1016/j.celrep.2016.09.058

Olanow, C. W. and Brundin, P. 2013. Parkinson’s disease and alpha synuclein: Is Parkinson’s disease a prion-like disorder? Movement Disorders 28(1):31−40. https://doi.org/10.1002/mds.25373

Papandreou, M. E. and Tavernarakis, N. 2017. Autophagy and the endo/exosomal pathways in health and disease. Biotechnology Journal 12(1). https://doi.org/10.1002/biot.201600175

Parkinson’s Disease, 2018. Retreived on April 18, 2018 from https://en.wikipedia.org/wiki/Parkinson%27s_disease

Pechstein, A., Gerth, F., Milosevic, I., Japel, M., Eichhorn-Grunig, M., Vorontsova, O., Bacetic, J., Maritzen, T., Shupliakov, O., Freund, C. and Haucke, V. 2015. Vesicle uncoating regulated by sh3-sh3 domain-mediated complex formation between endophilin and intersectin at synapses. EMBO Reports 16(2):232−239. https://doi.org/10.15252/embr.201439260

Razdorskaya, V. V., Voskresenskaya, O. N., Yudina, G. K. 2016. Parkinson’s disease in Russia: prevalence and incidence. Saratov Journal of Medical Scientific Research 12(3):379−384.

Rivero-Rios, P., Madero-Perez, J., Fernandez, B. and Hilfiker, S. 2016. Targeting the autophagy/lysosomal degradation pathway in parkinson’s disease. Current Neuropharmacology 14(3):238−249. https://doi.org/10.2174/1570159X13666151030103027

Saheki, Y. and De Camilli, P. 2012. Synaptic vesicle endocytosis. Cold Spring Harbor Perspectives in Biology 4(9):a005645. https://doi.org/10.1101/cshperspect.a005645

Schulz-Schaeffer, W. J. 2012. Neurodegeneration in parkinson disease: Moving lewy bodies out of focus. Neurology 79(24):2298−2299. https://doi.org/10.1212/WNL.0b013e318278b6a7

Scott, D. and Roy, S. 2012. Alpha-synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis. Journal of Neuroscience 32(30):10129−10135. https://doi.org/10.1523/JNEUROSCI.0535-12.2012

Scott, D. A., Tabarean, I., Tang, Y., Cartier, A., Masliah, E. and Roy, S. 2010. A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration. Journal of Neuroscience 30(24):8083−8095. https://doi.org/10.1523/JNEUROSCI.1091-10.2010

Shehadeh, L., Mitsi, G., Adi, N., Bishopric, N. and Papapetropoulos, S. 2009. Expression of lewy body protein septin 4 in postmortem brain of parkinson’s disease and control subjects. Movement Disorders 24(2):204−210. https://doi.org/10.1002/mds.22306

Soukup, S. F., Kuenen, S., Vanhauwaert, R., Manetsberger, J., Hernandez-Diaz, S., Swerts, J., Schoovaerts, N., Vilain, S., Gounko, N. V., Vints, K., Geens, A., De Strooper, B. and Verstreken, P. 2016. A lrrk2-dependent endophilina phosphoswitch is critical for macroautophagy at presynaptic terminals. Neuron 92(4):829−844. https://doi.org/10.1016/j.neuron.2016.09.037

Soukup, S. F. and Verstreken, P. 2017. Endoa/endophilin-a creates docking stations for autophagic proteins at synapses. Autophagy 13(5):971−972. https://doi.org/10.1080/15548627.2017.1286440

Staras, K., Branco, T., Burden, J. J., Pozo, K., Darcy, K., Marra, V., Ratnayaka, A. and Goda, Y. 2010. A vesicle superpool spans multiple presynaptic terminals in hippocampal neurons. Neuron 66(1):37−44. https://doi.org/10.1016/j.neuron.2010.03.020

Vargas, K. J., Makani, S., Davis, T., Westphal, C. H., Castillo, P. E. and Chandra, S. S. 2014. Synucleins regulate the kinetics of synaptic vesicle endocytosis. Journal of Neuroscience 34(28):9364−9376. https://doi.org/10.1523/JNEUROSCI.4787-13.2014

Wang, L., Das, U., Scott, D. A., Tang, Y., McLean, P. J. and Roy, S. 2014. Alpha-synuclein multimers cluster synaptic vesicles and attenuate recycling. Current Biology 24(19):2319−2326. https://doi.org/10.1016/j.cub.2014.08.027

Woods, W. S., Boettcher, J. M., Zhou, D. H., Kloepper, K. D., Hartman, K. L., Ladror, D. T., Qi, Z., Rienstra, C. M. and George, J. M. 2007. Conformation-specific binding of alpha-synuclein to novel protein partners detected by phage display and nmr spectroscopy. Journal of Biological Chemistry 282(47):34555−34567. https://doi.org/10.1074/jbc.M705283200

Zhang, Y., Gao, J., Chung, K. K., Huang, H., Dawson, V. L. and Dawson, T. M. 2000. Parkin functions as an e2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, cdcrel-1. Proceedings of the National Academy of Science, USA 97(24):13354−13359. https://doi.org/10.1073/pnas.240347797