QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 28 March 2006
doi: 10.1242/jcs.02878

This Article Figures Only Full Text Full Text (PDF) An erratum has been published All Versions of this Article: jcs.02878v1 119/8/1558    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Navarro-Lérida, I. Articles by Rodríguez-Crespo, I. Search for Related Content PubMed PubMed Citation Articles by Navarro-Lérida, I. Articles by Rodríguez-Crespo, I.

N-terminal palmitoylation within the appropriate amino acid environment conveys on NOS2 the ability to progress along the intracellular sorting pathways

¹ Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain
² Unidad de Citometría, Fundación CNIC, Instituto de Salud Carlos III, Melchor Fernández Almagro 3, 28040 Madrid, Spain

^* Author for correspondence (e-mail: nacho{at}bbm1.ucm.es)

Accepted 5 January 2006

We have analysed the mechanism by which palmitoylation permits the progression of nitric oxide synthase 2 (NOS2) along the ER-Golgi-TGN pathway. Introduction of an additional myristoylation site at the N-terminus of NOS2 resulted in a chimera that displayed an enhanced association with the particulate fraction and with the plasma membrane but did not display increased enzymatic activity. In the absence of palmitoylation, introduction of a surrogate myristoylation site resulted in a mutant NOS2 with only 25% activity compared with the wild-type enzyme. Hence, the novel surrogate myristoyl moiety not only failed to increase NOS2 activity when introduced in a wild-type sequence environment, but was also unable to rescue the inactive phenotype of the Cys3Ser mutant. Introduction of an additional palmitoylatable Cys at position 2 of the wild-type sequence resulted in a chimera that associated to a larger degree with membranes and displayed decreased activity. Our data indicate that palmitoylation of inducible NOS at position 3 exquisitely determines its transit along the secretory pathway following a route that cannot be mimicked by a surrogate myristoylation or by a palmitate at position 2. In addition, the exit of NOS2 from the TGN and the accumulation in the cellular plasma membrane per se did not correlate with increased ·NO synthesis.

Key words: NOS2, Palmitoylation, Caveolae, Nitric oxide

This article has been cited by other articles:

				I. Navarro-Lerida, M. Martinez-Moreno, I. Ventoso, A. Alvarez-Barrientos, and I. Rodriguez-Crespo Binding of CAP70 to Inducible Nitric Oxide Synthase and Implications for the Vectorial Release of Nitric Oxide in Polarized Cells Mol. Biol. Cell, July 1, 2007; 18(7): 2768 - 2777. [Abstract] [Full Text] [PDF]