Abstract #15

Trs130 is required for the specificity switch of a dual-Ypt/Rab GEF. Nava Segev¹, Nadya Morozova¹, Yongheng Liang¹, Andrei tokarev¹, Shu Chen¹, Vicki Sciora², Scott Emr². 1) Biological Sci, Lab Molec Biol, Univ Illinois, Chicago, Chicago, IL; 2) Callular and Molecular Medicine, Univ California, San Diego, CA.
   Intracellular trafficking in eukaryotes is regulated by Ypt/Rab GTPases. These GTPases are activated by guanine-nucleotide exchange factors (GEFs). When in the GTP-bound state, Ypt/Rabs interact with effectors that mediate individual steps of the protein trafficking pathways. An attractive possibility is that Ypt/Rabs and their accessory factors not only regulate the separate steps of protein transport pathways, but also coordinate these separate steps. Here, we propose a novel mechanism for such coordination in the Golgi. The modular multi-protein Golgi-associated complex, TRAPP, acts as a GEF for Ypt1 and Ypt31/32, the GTPases that regulate entry into and exit from the yeast Golgi, respectively. Trs130 is a TRAPP subunit that is found in late but not early Golgi, is conserved from yeast to man, and is a candidate for several human disorders. We show that Trs130 determines the specificity of the dual-GEF complex: it is required for switching the GEF activity of TRAPP from a Ypt1-GEF to a Ypt31/32-GEF. Unlike the wild-type complex, TRAPP purified from trs130ts mutant cells neither contains the Trs130 protein, nor acts as a Ypt31 GEF. However, its Ypt1-GEF activity is higher than that of the wild type. We propose that TRAPP acts as a Ypt1 GEF in early Golgi, whereas in late Golgi Trs130 is required for switching this activity off, and turning the Ypt31/32 GEF activity on. Such a switch-able dual-specificity GEF would ensure activation of Golgi Ypts at the correct cisterna, thereby coordinating entry into and exit from the Golgi apparatus.

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