COPII vesicles bud from the ER at ER Exit Sites (ERESs) to mediate the exit from the Endoplasmic Reticulum (ER) of newly synthesized proteins. Previously, we demonstrated that ER Stress rapidly impairs the anterograde transport to the Golgi complex and the formation of COPII vesicles (Amodio et al., 2009). In a recent work (Amodio et al., 2013) we found that the reduced permanence of Sec23a at the ERES could be the mean through which ER Stress modulates COPII assembling and vesicular trafficking. Sec23a is one of the component of the COPII vesicles coat and its GTPase activating function on Sar1 is one of the key mechanisms of COPII assembly. Interestingly, we found that during ER Stress the association to the ER membrane of Sec23a is reduced. Concomitantly, FRAP and FLIP analysis of Sec23a revealed that ER stress accelerates its recycling kinetics on ER membrane. These results prompted us to analyze the role of post-translational modifications of Sec23a in the regulation of its function during ER Stress. Surprisingly, we found that Sec23a is mono-ubiquitinated in mammalian cells on two different cysteines and that the induction of ER stress reduces the amount of mono-ubiquitinated Sec23a. The biological scope of Sec23a cysteine mono-ubiquitination has yet to be elucidated but recent evidences demonstrating that ubiquitination on cysteines regulates signal transduction and membrane translocation (Grou et al., 2008; Shannon and Weerapana, 2013) open new fields of investigation about Sec23a ubiquitination and modulation of COPII function.

Endoplasmic reticulum stress reduces COPII vesicles formation and modifies Sec23a cycling at ERESs G. Amodio1, O. Moltedo1, S. Franceschelli1, P. Remondelli2 1Dipartimento di Farmacia, Univ. of Salerno, Italy 2Dipartimento di Medicina e Chirurgia, Univ. of Salerno, Italy

AMODIO, GIUSEPPINA;MOLTEDO, Ornella;FRANCESCHELLI, Silvia;REMONDELLI, PAOLO
2014

Abstract

COPII vesicles bud from the ER at ER Exit Sites (ERESs) to mediate the exit from the Endoplasmic Reticulum (ER) of newly synthesized proteins. Previously, we demonstrated that ER Stress rapidly impairs the anterograde transport to the Golgi complex and the formation of COPII vesicles (Amodio et al., 2009). In a recent work (Amodio et al., 2013) we found that the reduced permanence of Sec23a at the ERES could be the mean through which ER Stress modulates COPII assembling and vesicular trafficking. Sec23a is one of the component of the COPII vesicles coat and its GTPase activating function on Sar1 is one of the key mechanisms of COPII assembly. Interestingly, we found that during ER Stress the association to the ER membrane of Sec23a is reduced. Concomitantly, FRAP and FLIP analysis of Sec23a revealed that ER stress accelerates its recycling kinetics on ER membrane. These results prompted us to analyze the role of post-translational modifications of Sec23a in the regulation of its function during ER Stress. Surprisingly, we found that Sec23a is mono-ubiquitinated in mammalian cells on two different cysteines and that the induction of ER stress reduces the amount of mono-ubiquitinated Sec23a. The biological scope of Sec23a cysteine mono-ubiquitination has yet to be elucidated but recent evidences demonstrating that ubiquitination on cysteines regulates signal transduction and membrane translocation (Grou et al., 2008; Shannon and Weerapana, 2013) open new fields of investigation about Sec23a ubiquitination and modulation of COPII function.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4653088
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