SUMOylation of synapsin Ia maintains synaptic vesicle availability and is reduced in an autism mutation

Nature Communications

Volumn 6, Issue , 2015, Pages

  Tang, Leo T H ^a   Craig, Tim J ^a   Henley, Jeremy M ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

SYNAPSIN I; SYNAPSIN IA; UNCLASSIFIED DRUG; SYNAPSIN;

CELLS AND CELL COMPONENTS; MEMBRANE; MOLECULAR ANALYSIS; MUTATION; NERVOUS SYSTEM DISORDER; PROTEIN;

ACTIN FILAMENT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUTISM; CONSENSUS SEQUENCE; CONTROLLED STUDY; DIMERIZATION; ELECTRIC FIELD; EMBRYO; EPILEPSY; EXOCYTOSIS; IMMUNOPRECIPITATION; NERVE ENDING; NERVE STIMULATION; NONHUMAN; PHENOTYPE; PROTEIN CONFORMATION; PROTEIN PROTEIN INTERACTION; RAT; SEQUENCE ALIGNMENT; SUMOYLATION; SYNAPSE VESICLE; SYNAPTIC TRANSMISSION; ANIMAL; BRAIN CORTEX; CYTOLOGY; GENETICS; HIPPOCAMPUS; HUMAN; METABOLISM; MUTATION; NERVE CELL; SYNAPSE; WISTAR RAT;

ANIMALS; AUTISTIC DISORDER; CEREBRAL CORTEX; EPILEPSY; EXOCYTOSIS; HIPPOCAMPUS; HUMANS; MUTATION; NEURONS; RATS; RATS, WISTAR; SUMOYLATION; SYNAPSES; SYNAPSINS; SYNAPTIC TRANSMISSION; SYNAPTIC VESICLES;

EID: 84955247486     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8728     Document Type: Article

References (44)

1. Rizzoli, S. O. & Betz, W. J. Synaptic vesicle pools. Nat. Rev. Neurosci. 6, 57-69 (2005).
2. Ceccaldi, P. E. et al. Dephosphorylated synapsin I anchors synaptic vesicles to actin cytoskeleton: an analysis by videomicroscopy. J. Cell Biol. 128, 905-912 (1995).
3. Cesca, F., Baldelli, P., Valtorta, F. & Benfenati, F. The synapsins: key actors of synapse function and plasticity. Prog. Neurobiol. 91, 313-348 (2010).
4. Bykhovskaia, M. Synapsin regulation of vesicle organization and functional pools. Semin. Cell Dev. Biol. 22, 387-392 (2011).
5. Verstegen, A. M. et al. Phosphorylation of synapsin I by cyclin-dependent kinase-5 sets the ratio between the resting and recycling pools of synaptic vesicles at hippocampal synapses. J. Neurosci. 34, 7266-7280 (2014).
6. Jovanovic, J. N. et al. Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals. J. Neurosci. 21, 7944-7953 (2001).
7. Wilkinson, K. A., Nakamura, Y. & Henley, J. M. Targets and consequences of protein SUMOylation in neurons. Brain Res. Rev. 64, 195-212 (2010).
8. Craig, T. J. & Henley, J. M. Protein SUMOylation in spine structure and function. Curr. Opin. Neurobiol. 22, 480-487 (2012).
9. Luo, J. et al. Receptor trafficking and the regulation of synaptic plasticity by SUMO. Neuromol. Med. 15, 692-706 (2013).
10. Feligioni, M., Nishimune, A. & Henley, J. M. Protein SUMOylation modulates calcium influx and glutamate release from presynaptic terminals. Eur. J. Neurosci. 29, 1348-1356 (2009).
11. Guo, C. & Henley, J. Wrestling with stress: roles of protein SUMOylation and deSUMOylation in cell stress response. IUBMB Life 66, 71-77 (2014).
12. Girach, F., Craig, T. J., Rocca, D. L. & Henley, J. M. RIM1alpha SUMOylation is required for fast synaptic vesicle exocytosis. Cell Rep. 5, 1294-1301 (2013).
13. Hilfiker, S. et al. Two sites of action for synapsin domain E in regulating neurotransmitter release. Nat. Neurosci. 1, 29-35 (1998).
14. Monaldi, I. et al. The highly conserved synapsin domain E mediates synapsin dimerization and phospholipid vesicle clustering. Biochem. J. 426, 55-64 (2010).
15. Sudhof, T. C. et al. Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins. Science 245, 1474-1480 (1989).
16. Candiani, S. et al. The synapsin gene family in basal chordates: evolutionary perspectives in metazoans. BMC Evol. Biol. 10, 32 (2010).
17. Burrone, J., Li, Z. & Murthy, V. N. Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptop Hluorin. Nat. Protoc. 1, 2970-2978 (2006).
18. Ikeda, K. & Bekkers, J. M. Counting the number of releasable synaptic vesicles in a presynaptic terminal. Proc. Natl Acad. Sci USA 106, 2945-2950 (2009).
19. Li, L. et al. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc. Natl Acad. Sci. USA 92, 9235-9239 (1995).
20. Rosahl, T. W. et al. Essential functions of synapsins I and II in synaptic vesicle regulation [see comments]. Nature 375, 488-493 (1995).
21. Ryan, T. A., Li, L., Chin, L. S., Greengard, P. & Smith, S. J. Synaptic vesicle recycling in synapsin I knock-out mice. J. Cell Biol. 134, 1219-1227 (1996).
22. Buchner, A. et al. Sumoylation of p35 modulates p35/cyclin-dependent kinase (Cdk) 5 complex activity. Neuromol. Med. 17, 12-23 (2015).
23. Geerts, C. J., Jacobsen, L., van de Bospoort, R., Verhage, M. & Groffen, A. J. Tomosyn interacts with the SUMO E3 ligase PIASgamma. PLoS ONE 9, e91697 (2014).
24. Uchimura, Y., Nakamura, M., Sugasawa, K., Nakao, M. & Saitoh, H. Overproduction of eukaryotic SUMO-1- and SUMO-2-conjugated proteins in Escherichia coli. Anal. Biochem. 331, 204-206 (2004).
25. Wilkinson, K. A., Nishimune, A. & Henley, J. M. Analysis of SUMO-1 modification of neuronal proteins containing consensus SUMOylation motifs. Neurosci. Lett. 436, 239-244 (2008).
26. Benfenati, F., Bahler, M., Jahn, R. & Greengard, P. Interactions of synapsin I with small synaptic vesicles: distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins. J. Cell Biol. 108, 1863-1872 (1989).
27. Benfenati, F., Valtorta, F., Bahler, M. & Greengard, P. Synapsin I, a neuronspecific phosphoprotein interacting with small synaptic vesicles and F-actin. Cell Biol. Int. Rep. 13, 1007-1021 (1989).
28. Gareau, J. R. & Lima, C. D. The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nat. Rev. Mol. Cell Biol. 11, 861-871 (2011).
29. Kerscher, O. SUMO junction-what's your function? New insights through SUMO-interacting motifs. EMBO Rep. 8, 550-555 (2007).
30. Benfenati, F., Neyroz, P., Bahler, M., Masotti, L. & Greengard, P. Time-resolved fluorescence study of the neuron-specific phosphoprotein synapsin I. Evidence for phosphorylation-dependent conformational changes. J. Biol. Chem. 265, 12584-12595 (1990).
31. Gitler, D. et al. Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J. Neurosci. 24, 11368-11380 (2004).
32. Tang, Y. et al. Fast vesicle transport is required for the slow axonal transport of synapsin. J. Neurosci. 33, 15362-15375 (2013).
33. Easley-Neal, C., Fierro, J. Jr., Buchanan, J. & Washbourne, P. Late recruitment of synapsin to nascent synapses is regulated by Cdk5. Cell Rep. 3, 1199-1212 (2013).
34. Fassio, A. et al. SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function. Hum. Mol. Genet. 20, 2297-2307 (2011).
35. Chi, P., Greengard, P. & Ryan, T. A. Synapsin dispersion and reclustering during synaptic activity. Nat. Neurosci. 4, 1187-1193 (2001).
36. Wilkinson, K. A. & Henley, J. M. Mechanisms, regulation and consequences of protein SUMOylation. Biochem. J. 428, 133-145 (2010).
37. Garcia, C. C. et al. Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy. J. Med. Genet. 41, 183-186 (2004).
38. Etholm, L. & Heggelund, P. Seizure elements and seizure element transitions during tonic-clonic seizure activity in the synapsin I/II double knockout mouse: a neuroethological description. Epilepsy Behav. 14, 582-590 (2009).
39. Greco, B. et al. Autism-related behavioral abnormalities in synapsin knockout mice. Behav. Brain Res. 251, 65-74 (2013).
40. Lignani, G. et al. Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum. Mol. Genet. 22, 2186-2199 (2013).
41. Martin, S. & Henley, J. M. Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways. EMBO J. 23, 4749-4759 (2004).
42. Craig, T. J. & Henley, J. M. SUMOylation, Arc and the regulation homeostatic synaptic scaling: implications in health and disease. Commun. Integr. Biol. 5, 634-636 (2012).
43. Huttner, W. B., Schiebler, W., Greengard, P. & De Camilli, P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation. J. Cell Biol. 96, 1374-1388 (1983).
44. Uchimura, Y., Nakao, M. & Saitoh, H. Generation of SUMO-1 modified proteins in E. coli: towards understanding the biochemistry/structural biology of the SUMO-1 pathway. FEBS Lett. 564, 85-90 (2004).