Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 317 (5840): 947-951

Copyright © 2007 by the American Association for the Advancement of Science

Spatial Regulation of an E3 Ubiquitin Ligase Directs Selective Synapse Elimination

Mei Ding,1 Dan Chao,1,2 George Wang,1 Kang Shen1,2*

Abstract: Stereotyped synaptic connectivity can arise both by precise recognition between appropriate partners during synaptogenesis and by selective synapse elimination. The molecular mechanisms that underlie selective synapse removal are largely unknown. We found that stereotyped developmental elimination of synapses in the Caenorhabditis elegans hermaphrodite-specific motor neuron (HSNL) was mediated by an E3 ubiquitin ligase, a Skp1–cullin–F-box (SCF) complex composed of SKR-1 and the F-box protein SEL-10. SYG-1, a synaptic adhesion molecule, bound to SKR-1 and inhibited assembly of the SCF complex, thereby protecting nearby synapses. Thus, subcellular regulation of ubiquitin-mediated protein degradation contributes to precise synaptic connectivity through selective synapse elimination.

1 Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
2 Neuroscience Program, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: kangshen{at}stanford.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cell biology in neuroscience: Cellular and molecular mechanisms underlying presynapse formation.
P. H. Chia, P. Li, and K. Shen (2013)
J. Cell Biol. 203, 11-22
   Abstract »    Full Text »    PDF »
The role of ubiquitin-mediated pathways in regulating synaptic development, axonal degeneration and regeneration: insights from fly and worm.
X. Tian and C. Wu (2013)
J. Physiol. 591, 3133-3143
   Abstract »    Full Text »    PDF »
The C. elegans F-box proteins LIN-23 and SEL-10 antagonize centrosome duplication by regulating ZYG-1 levels.
N. Peel, M. Dougherty, J. Goeres, Y. Liu, and K. F. O'Connell (2012)
J. Cell Sci. 125, 3535-3544
   Abstract »    Full Text »    PDF »
A Transcriptional Program Promotes Remodeling of GABAergic Synapses in Caenorhabditis elegans.
S. C. Petersen, J. D. Watson, J. E. Richmond, M. Sarov, W. W. Walthall, and D. M. Miller III (2011)
J. Neurosci. 31, 15362-15375
   Abstract »    Full Text »    PDF »
Two types of chloride transporters are required for GABAA receptor-mediated inhibition in C. elegans.
A. Bellemer, T. Hirata, M. F. Romero, and M. R. Koelle (2011)
EMBO J. 30, 1852-1863
   Abstract »    Full Text »    PDF »
The ubiquitin-proteasome pathway and synaptic plasticity.
A. N. Hegde (2010)
Learn. Mem. 17, 314-327
   Abstract »    Full Text »    PDF »
A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis.
E. Neumann-Haefelin, A. Kramer-Zucker, K. Slanchev, B. Hartleben, F. Noutsou, K. Martin, N. Wanner, A. Ritter, M. Godel, P. Pagel, et al. (2010)
Hum. Mol. Genet. 19, 2347-2359
   Abstract »    Full Text »    PDF »
A Role for the Ubiquitin-Proteasome System in Activity-Dependent Presynaptic Silencing.
X. Jiang, P. E. Litkowski, A. A. Taylor, Y. Lin, B. J. Snider, and K. L. Moulder (2010)
J. Neurosci. 30, 1798-1809
   Abstract »    Full Text »    PDF »
Cell Adhesion, the Backbone of the Synapse: "Vertebrate" and "Invertebrate" Perspectives.
N. Giagtzoglou, C. V. Ly, and H. J. Bellen (2009)
Cold Spring Harb Perspect Biol 1, a003079
   Abstract »    Full Text »    PDF »
Regulation of the Proteasome by Neuronal Activity and Calcium/Calmodulin-dependent Protein Kinase II.
S. N. Djakovic, L. A. Schwarz, B. Barylko, G. N. DeMartino, and G. N. Patrick (2009)
J. Biol. Chem. 284, 26655-26665
   Abstract »    Full Text »    PDF »
The Potassium Chloride Cotransporter KCC-2 Coordinates Development of Inhibitory Neurotransmission and Synapse Structure in Caenorhabditis elegans.
J. E. Tanis, A. Bellemer, J. J. Moresco, B. Forbush, and M. R. Koelle (2009)
J. Neurosci. 29, 9943-9954
   Abstract »    Full Text »    PDF »
RSY-1 Is a Local Inhibitor of Presynaptic Assembly in C. elegans.
M. R. Patel and K. Shen (2009)
Science 323, 1500-1503
   Abstract »    Full Text »    PDF »
Think locally: control of ubiquitin-dependent protein degradation in neurons.
A. Segref and T. Hoppe (2009)
EMBO Rep. 10, 44-50
   Abstract »    Full Text »    PDF »
Genomic Analysis of Drosophila Neuronal Remodeling: A Role for the RNA-Binding Protein Boule as a Negative Regulator of Axon Pruning.
E. D. Hoopfer, A. Penton, R. J. Watts, and L. Luo (2008)
J. Neurosci. 28, 6092-6103
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: Synapses Here and Not Everywhere.
D. M. Miller (2007)
Science 317, 907-908
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882