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Rapid Ca2+-dependent Decrease of Protein Ubiquitination at Synapses

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Specialty Science
Date 2003 Dec 6
PMID 14657369
Citations 61
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Abstract

Protein ubiquitination has been implicated in the regulation of axonal growth and synaptic plasticity as well as in the pathogenesis of neurodegenerative diseases. Here we show that depolarization-dependent Ca2+ influx into synaptosomes produces a global, rapid (range of seconds), and reversible decrease of the ubiquitinated state of proteins, which correlates with the Ca2+-dependent dephosphorylation of several synaptic proteins. A similar general decrease in protein ubiquitination was observed in nonneuronal cells on Ca2+ entry induced by ionomycin. Both in synaptosomes and in nonneuronal cells, this decrease was blocked by FK506 (a calcineurin antagonist). Proteins whose ubiquitinated state was decreased include epsin 1, a substrate for the deubiquitinating enzyme fat facets/FAM, which we show here to be concentrated at synapses. These results reveal a fast regulated turnover of protein ubiquitination. In nerve terminals, protein ubiquitination may play a role both in the regulation of synaptic function, including vesicle traffic, and in the coordination of protein turnover with synaptic use.

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References
1.
Nicholls D, Sihra T . Synaptosomes possess an exocytotic pool of glutamate. Nature. 1986; 321(6072):772-3. DOI: 10.1038/321772a0. View

2.
Chan S, Mattson M . Caspase and calpain substrates: roles in synaptic plasticity and cell death. J Neurosci Res. 1999; 58(1):167-90. View

3.
Saito Y, Kawashima S . The neurite-initiating effect of a tripeptide aldehyde protease inhibitor on PC12h cells. J Biochem. 1989; 106(6):1035-40. DOI: 10.1093/oxfordjournals.jbchem.a122960. View

4.
De Camilli P, Benfenati F, Valtorta F, Greengard P . The synapsins. Annu Rev Cell Biol. 1990; 6:433-60. DOI: 10.1146/annurev.cb.06.110190.002245. View

5.
Erecinska M, Nelson D, Chance B . Depolarization-induced changes in cellular energy production. Proc Natl Acad Sci U S A. 1991; 88(17):7600-4. PMC: 52349. DOI: 10.1073/pnas.88.17.7600. View