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Yeast Npi3/Bro1 is involved in ubiquitin‐dependent control of permease trafficking
Author(s) -
Springael Jean-Yves,
Nikko Elina,
André Bruno,
Marini Anne-Marie
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02586-3
Subject(s) - permease , ubiquitin , biochemistry , deubiquitinating enzyme , microbiology and biotechnology , vacuole , ubiquitin ligase , saccharomyces cerevisiae , biology , transport protein , chemistry , mutant , yeast , gene , cytoplasm
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 NH 4 + ‐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.