Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites

Science

Volumn 304, Issue 5678, 2004, Pages 1815-1819

  Fremeau Jr , Robert T ^a   Kam, Kaiwen ^a   Qureshi, Yayyaba ^b   Johnson, Juliette ^a   Copenhagen, David R ^a   Storm Mathisen, Jon ^b   Chaudhry, Farrukh A ^b   Nicoll, Roger A ^a   Edwards, Robert H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

[No Author keywords available]

Indexed keywords

GENES; MEMBRANES; NEUROLOGY; PLASTICITY;

CELL POPULATIONS; NERVE TERMINAL; VESICULAR GLUTAMATE TRANSPORTERS (VGLUTS);

BRAIN;

GLUTAMATE TRANSPORTER; GLUTAMATE TRANSPORTER 2; UNCLASSIFIED DRUG; VESICULAR GLUTAMATE TRANSPORTER 1;

BIOLOGY;

ANIMAL CELL; ARTICLE; CELL POPULATION; CONTROLLED STUDY; EXOCYTOSIS; GENE; GENE INACTIVATION; GENE SILENCING; HIPPOCAMPUS; MOUSE; NERVE ENDING; NEUROTRANSMISSION; NEUROTRANSMITTER RELEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN SECRETION; PROTEIN TARGETING; SYNAPSE VESICLE; SYNAPTIC TRANSMISSION; VGLUT1 GENE;

ANIMALS; ANIMALS, NEWBORN; BRAIN; CARRIER PROTEINS; CELL MEMBRANE; CELLS, CULTURED; CEREBELLUM; EXCITATORY POSTSYNAPTIC POTENTIALS; GLUTAMIC ACID; HIPPOCAMPUS; IN SITU HYBRIDIZATION; MEMBRANE TRANSPORT PROTEINS; MICE; MICE, KNOCKOUT; NERVE TISSUE PROTEINS; NEURONS; PATCH-CLAMP TECHNIQUES; PURKINJE CELLS; PYRAMIDAL CELLS; SYNAPSES; SYNAPTIC TRANSMISSION; SYNAPTIC VESICLES; VESICULAR GLUTAMATE TRANSPORT PROTEIN 1; VESICULAR GLUTAMATE TRANSPORT PROTEIN 2; VESICULAR TRANSPORT PROTEINS;

ANIMALIA;

EID: 2942707811     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1097468     Document Type: Article

References (31)

1. P. R. Maycox, T. Deckwerth, J. W. Hell, R. Jahn, J. Biol. Chem. 263, 15423 (1988).
2. M. D. Carlson, P. E. Kish, T. Ueda, J. Biol. Chem. 264, 7369 (1989).
3. R. Y. Lee, E. R. Sawin, M. Chalfie, H. R. Horvitz, L. Avery, J. Neurosci. 19, 159 (1999).
4. E. E. Bellocchio, R. J. Reimer, R. T. J. Fremeau, R. H. Edwards, Science 289, 957 (2000).
5. S. Takamori, J. S. Rhee, C. Rosenmund, R. Jahn, Nature 407, 189 (2000).
6. R. T. Fremeau Jr. et al., Neuron 31, 247 (2001).
7. S. Takamori, J. S. Rhee, C. Rosenmund, R. Jahn, J. Neurosci. 21, RC182 (2001).
8. E. Herzog et al., J. Neurosci. 21, RC181 (2001).
9. B. Ni, P. R. Rosteck, N. S. Nadi, S. M. Paul, Proc. Natl. Acad. Sci. U.S.A. 91, 5607 (1994).
10. Y. Aihara et al., J. Neurochem. 74, 2622 (2000).
11. E. E. Bellocchio et al., J. Neurosci. 18, 8648 (1998).
12. H. Varoqui, M. K. Schafer, H. Zhu, E. Weihe, J. D. Erickson, J. Neurosci. 22, 142 (2002).
13. C. Gras et al., J. Neurosci. 22, 5442 (2002).
14. R. T. Fremeau Jr. et al., Proc. Natl. Acad. Sci. U.S.A. 99, 14488 (2002).
15. M. K. Schafer, H. Varoqui, N. Defamie, E. Weihe, J. D. Erickson, J. Biol. Chem. 277, 50734 (2002).
16. If both isoforms were present on the same veside, the loss of VGLUT1 should have reduced quantal size, assuming that the amount of transporter expressed limits the rate of veside filling. If, however, a single VGLUT protein suffices to fill a veside to thermodynamic equilibrium, and if many vesides contain VGLUT2 as well as VGLUT1, the knockout could not have substantially reduced excitatory transmission. A large number of synaptic vesides must therefore contain only one isoform.
17. N. A. Hessler, A. M. Shirke, R. Malinow, Nature 366, 569 (1993).
18. C. Rosenmund, J. D. Clements, G. L. Westbrook, Science 262, 754 (1993).
19. S. Takamori, P. Malherbe, C. Broger, R. Jahn, EMBO Rep. 3, 798 (2002).
20. C. Rosenmund et al., Neuron 33, 411 (2002).
21. The ratio of vesicles >100 nm from the cell membrane/vesicles. <100 nm from the membrane was 1.73 ± 0.21 (mean ± SEM) in the wild type and 0.88 ± 0.14 in the knockout based on all the data. P = 0.004 by analysis of variance (General Linear Model, MINITAB).
22. T. W. Rosahl et al., Nature 375, 488 (1995).
23. T. A. Ryan, L. Li, L. S. Chin, P. Greengard, S. J. Smith, J. Cell Biol. 134, 1219 (1996).
24. Q. Zhou, C. C. H. Petersen, R. A. Nicoll, J. Physiol. 525, 195 (2000).
25. R. L. Parsons, M. A. Calupca, L. A. Merriam, C. Prior, J. Neurophysiol. 81, 2696 (1999).
26. M. Verhage et al., Science 287, 864 (2000).
27. I. Augustin, C. Rosenmund, T. C. Sudhof, N. Brose, Nature 400, 457 (1999).
28. W. D. Altrock et al., Neuron 37, 787 (2003).
29. Although the altered morphology of excitatory terminals might be thought to contribute to the enhanced short-term depression observed in VGLUT1 knockout mice, the changes presumably occur at silent synapses that would otherwise have expressed VGLUT1, rather than the functional synapses expressing VGLUT2.
30. T. Miyazaki, M. Fukaya, H. Shimizu, M. Watanabe, Eur. J. Neurosci. 17, 2563 (2003).
31. We thank N. Killeen, N. Calakos, D. House, V. Stein, C. Zhou, and G. Li for assistance, and M. Scanziani, H. Li, and members of the Edwards, Nicoll, and Pleasure laboratories for suggestions. T.Q., F.A.C., and J.S.-M. were supported by the Norwegian Research Council and the European Union. K.K. is supported by NSF, J.J. and D.R.C. by NIH, R.T.F. by NINDS, and R.H.E. by the National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, and the Mathers Foundation. R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research and is supported by the NIH and the Bristol-Myers Squibb Co.