999 resultados para 331.133


Relevância:

20.00% 20.00%

Publicador:

Resumo:

Recurso electrónico. Valencia: BVNP, 2014

Relevância:

20.00% 20.00%

Publicador:

Resumo:

TGN38 is one of the few known resident integral membrane proteins of the trans-Golgi network (TGN). Since it cycles constitutively between the TGN and the plasma membrane, TGN38 is ideally suited as a model protein for the identification of post-Golgi trafficking motifs. Several studies, employing chimeric constructs to detect such motifs within the cytosolic domain of TGN38, have identified the sequence 333YQRL336 as an autonomous signal capable of localizing reporter proteins to the TGN. In addition, one group has found that an upstream serine residue, S331, may also play a role in TGN38 localization. However, the nature and degree of participation of S331 in the localization of TGN38 remain uncertain, and the effect has been studied in chimeric constructs only. Here we investigate the role of S331 in the context of full-length TGN38. Mutations that abolish the hydroxyl moiety at position 331 (A, D, and E) lead to missorting of endocytosed TGN38 to the lysosome. Conversely, mutation of S331 to T has little effect on the endocytic trafficking of TGN38. Together, these findings indicate that the S331 hydroxyl group has a direct or indirect effect on the ability of the cytosolic tail of TGN38 to interact with trafficking and/or sorting machinery at the level of the early endosome. In addition, mutation of S331 to either A or D results in increased levels of TGN38 at the cell surface. The results confirm that S331 plays a critical role in the intracellular trafficking of TGN38 and further reveal that TGN38 undergoes a signal-mediated trafficking step at the level of the endosome.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

There has been an increasing use of direct democracy in the form of referendums on aspects of European integration. Two such referendums have been held in Ireland in 2008 and 2009 with the outcome changing from a No to a Yes vote. This paper addresses the question of what explains the change in outcome in two referendums on essentially the same document. It will do so by looking at the role of the campaign in providing information and hence reducing uncertainty, the importance of issue frames and the impact of domestic considerations on vote choice. It is suggested that there has not been a change in underlying attitudes but a change in how the Irish electorate weighed the same factors differently at both referendums. In addition, a change in economic conditions at the time of the second referendum also had an effect on how voters decided the second time around.