Yeast Npi3/Bro1 is involved in ubiquitin‐dependent control of permease trafficking

FEBS Letters

André, Bruno¹  Nikko, Elina¹  Marini, Anne-Marie¹  Springael, Jean-Yves¹ 

[1] Laboratoire de Physiologie Cellulaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, P.O. Box 300, Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium

关键词: Npi3/Bro1;    Ubiquitin;    Permease;    Traffic;    Yeast;   

DOI  :  10.1016/S0014-5793(02)02586-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The membrane traffic and stability of the general amino acid permease Gap1 of Saccharomyces cerevisiae are under nitrogen control. Addition of a preferential nitrogen source such as ammonium to cells growing on a poor nitrogen source induces internalization of the permease and its subsequent degradation in the vacuole. This down-regulation requires ubiquitination of Gap1 through a process involving ubiquitin ligase Npi1/Rsp5, ubiquitin hydrolase Npi2/Doa4, and Bul1/2, two Npi1/Rsp5 interacting proteins. Here we report that yet another protein, Npi3, is involved in the regulation of Gap1 trafficking. We show that Npi3 is required for NH₄ ⁺-induced down-regulation of Gap1, and particularly for efficient ubiquitination of the permease. Npi3 plays a pleiotropic role in permease down-regulation, since it is also involved in ubiquitination and stress-induced down-regulation of the uracil permease Fur4 and in glucose-induced degradation of hexose transporters Hxt6/7. We further provide evidence that Npi3 is required for direct vacuolar sorting of neosynthesized Gap1 permease as it occurs in npr1 mutant cells. NPI3 is identical to BRO1, a gene encoding a protein of unknown biochemical function and recently proposed to be involved in protein turnover. Npi3/Bro1 homologues include fungal proteins required for proteolytic cleavage of zinc finger proteins and the mouse Aip1 protein involved in apoptosis. We propose that proteins of the Npi3/Bro1 family, including homologues from higher species, may play a conserved role in ubiquitin-dependent control of membrane protein trafficking.

【 授权许可】

Unknown