DOI: 10.1126/science.1117541. Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth

Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth

10.1126/science.1117541

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The molecular pathways involved in retrograde signal transduction at synapses and the function of retrograde communication are poorly understood. Here, we demonstrate that postsynaptic calcium 2 + ion (Ca 2+ ) influx through glutamate receptors and subsequent postsynaptic vesicle fusion trigger a robust induction of presynaptic miniature release after high-frequency stimulation at Drosophila neuromuscular junctions. An isoform of the synaptotagmin family, synaptotagmin 4 (Syt 4), serves as a postsynaptic Ca 2+ sensor to release retrograde signals that stimulate enhanced presynaptic function through activation of the cyclic adenosine monophosphate (cAMP)–cAMP-dependent protein kinase pathway. Postsynaptic Ca 2+ influx also stimulates local synaptic differentiation and growth through Syt 4–mediated retrograde signals in a synapse-specific manner.

Bibliography

Yoshihara, M., Adolfsen, B., Galle, K. T., & Littleton, J. T. (2005). Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth. Science, 310(5749), 858â863.

Authors 4

Motojiro Yoshihara (first)
Bill Adolfsen (additional)
Kathleen T. Galle (additional)
J. Troy Littleton (additional)

References 32 Referenced 137

10.1038/361031a0
10.1126/science.1067020
10.1016/j.conb.2004.05.011
10.1016/S0896-6273(00)80081-1
Experimental procedures can be found on Science Online.
10.1016/0306-4522(89)90091-2
10.1016/S0166-2236(03)00072-9
10.1002/neu.480140305
10.1016/S0092-8674(00)00183-5
10.1016/0092-8674(94)90556-8
10.1016/S0896-6273(02)01065-6
10.1083/jcb.200312054
10.1038/28190
10.1101/gad.3.1.85
10.1038/23462
10.1523/JNEUROSCI.19-07-02432.1999
10.1101/gad.7.7a.1229
10.1016/0896-6273(93)90178-T
10.1523/JNEUROSCI.20-22-08315.2000
10.1523/JNEUROSCI.17-21-08408.1997
10.1523/JNEUROSCI.19-08-03023.1999
10.1126/science.1681587
10.1016/0092-8674(95)90414-X
10.1073/pnas.92.6.2164
M. Yoshihara et al. data not shown.
10.1016/0092-8674(95)90509-X
10.1523/JNEUROSCI.12-02-00644.1992
10.1016/S0896-6273(00)80372-4
D. O. Hebb The Organization of Behavior (Wiley New York 1949).
10.1038/385533a0
10.1016/S0092-8674(00)80484-5
We are grateful to S. Waddell for fruitful discussions providing Drosophila strains and critical reading of the manuscript; M. Sheng M. Bear S. Tonegawa C. Quinn M. Sur and E. Montana for critical reading of the manuscript; K. Ikeda for useful discussion; C.-F. Wu for technical advice; G. Miesenbock for providing pHluorin DNA; N. Harden and E. Buchner for antibodies; and A. DiAntonio D. Kalderon J. Kiger S. Thor K. Schulze J. Phillips G. Davis C. S. Goodman and the Bloomington Stock Center for providing Drosophila strains. This work was supported by grants from the NIH the Human Frontiers Science Program Organization the Packard Foundation and the Searle Scholars Program.

Dates

Type	When
Created	19 years, 10 months ago (Nov. 3, 2005, 4:48 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:09 p.m.)
Indexed	1 month, 1 week ago (July 27, 2025, 3:21 a.m.)
Issued	19 years, 10 months ago (Nov. 4, 2005)
Published	19 years, 10 months ago (Nov. 4, 2005)
Published Print	19 years, 10 months ago (Nov. 4, 2005)

Funders 0

None

BibTeX

@article{Yoshihara_2005, title={Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth}, volume={310}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1117541}, DOI={10.1126/science.1117541}, number={5749}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Yoshihara, Motojiro and Adolfsen, Bill and Galle, Kathleen T. and Littleton, J. Troy}, year={2005}, month=nov, pages={858–863} }

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