Prencipe, Libera (2008) The role of GRASP65 and GRASP55 in C-terminal valine-dependent transport to the cell surface of transmembrane proteins. [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Uncontrolled Keywords: GRASP65/GRASP55/CD8-alpha/Frizzled4/FEVR
Date Deposited: 13 Nov 2009 18:25
Last Modified: 30 Apr 2014 19:36
URI: http://www.fedoa.unina.it/id/eprint/3353

Abstract

The Golgi-matrix proteins GRASP65 and GRASP55 have recognized roles in maintaining the architecture of the Golgi complex, in mitotic progression and in unconventional protein secretion while, surprisingly, they have been shown to be dispensable for the transport of commonly used reporter cargo proteins along the secretory pathway. However, it is becoming increasingly clear that many trafficking machineries operate in a cargo-specific manner, thus we have investigated whether GRASPs may control the trafficking of selected classes of cargoes. We have taken into consideration the C-terminal valine bearing receptors CD8 and Frizzled4 that we show bind directly to the PDZ domains of GRASP65 and GRASP55. We demonstrate that both GRASPs are needed sequentially for the efficient transport to and through the Golgi complex of these receptors, thus highlighting a novel role for the GRASPs in membrane trafficking. Our results open new perspectives for our understanding of the regulation of surface expression of a class of membrane proteins, and suggests the causal mechanisms of a dominant form of autosomal human familial exudative vitreoretinopathy that arises from Frizzled4 mutation involving its C-terminal valine.

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