Abstract
The prenylated Rab acceptor (PRA) 1 is a protein that binds prenylated Rab GTPases and inhibits their removal from the membrane by GDI. We describe here the isolation of a second isoform that can also bind Rab GTPases in a guanine nucleotide-independent manner. The two PRA isoforms showed distinct intracellular localization with PRA1 localized primarily to the Golgi complex and PRA2 to the endoplasmic reticulum (ER) compartment. The localization signal was mapped to the COOH-terminal domain of the two proteins. A DXEE motif served to target PRA1 to the Golgi. Mutation of any one of the acidic residues within this motif resulted in significant retention of PRA1 in the ER compartment. Moreover, the introduction of a di-acidic motif to the COOH-terminal domain of PRA2 resulted in partial localization to the Golgi complex. The domain responsible for ER localization of PRA2 was also confined to the carboxyl terminus. Our results showed that these sorting signals were primarily responsible for the differential localization of the two PRA isoforms.
Highlights
Rab GTPases are a family of 20 –29-kDa Ras-like GTPases localized to unique intracellular organelles [1,2,3,4,5,6,7]
When combined with the previous observation, these results suggest that the COOH-terminal domain of PRA2 can partially target proteins to the membrane and that transport of PRA1 to the Golgi complex required additional domains such as ones that can functionally interact with Rab or VAMP2
Northern analysis showed that PRA2 is ubiquitously expressed in all tissues, suggesting that it might participate in general membrane trafficking events
Summary
The prenylated Rab acceptor (PRA) 1 is a protein that binds prenylated Rab GTPases and inhibits their removal from the membrane by GDI. Rab GTPases are a family of 20 –29-kDa Ras-like GTPases localized to unique intracellular organelles [1,2,3,4,5,6,7] They cycle through an active membrane-bound GTP- and inactive cytosolic GDP-bound states. We describe here the isolation of a second PRA isoform that shares many similarities to PRA1 including overall physical properties, tissue distribution, and broad binding specificity toward the Rab GTPases. It differs from PRA1 in its subcellular localization. We showed that the localization signal resides in the COOH-terminal region of the proteins
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