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.
Rapid Ca2+-dependent decrease of protein ubiquitination at synapses / H. Chen, S. Polo, P.P. Di Fiore, P.V. De Camilli. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 100:25(2003 Dec 09), pp. 14908-14913.
|Titolo:||Rapid Ca2+-dependent decrease of protein ubiquitination at synapses|
POLO, SIMONA LAURA ANNA (Secondo)
DI FIORE, PIER PAOLO (Penultimo)
|Parole Chiave:||Animals; Synapses; Calcium; Electrophoresis, Polyacrylamide Gel; Synaptosomes; Temperature; Brain; Potassium; Tacrolimus; RNA, Small Interfering; Precipitin Tests; Rats; DNA, Complementary; Blotting, Western; Transfection; Cells, Cultured; Time Factors; Ubiquitin|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||9-dic-2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.2136625100|
|Appare nelle tipologie:||01 - Articolo su periodico|