Premium
The arrestin‐like protein ArtA is essential for ubiquitination and endocytosis of the UapA transporter in response to both broad‐range and specific signals
Author(s) -
Karachaliou Mayia,
Amillis Sotiris,
Evangelinos Minoas,
Kokotos Alexandros C.,
Yalelis Vassilis,
Diallinas George
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12184
Subject(s) - endocytosis , biology , ubiquitin , microbiology and biotechnology , transporter , biochemistry , receptor , gene
Summary We investigated the role of all arrestin‐like proteins of A spergillus nidulans in respect to growth, morphology, sensitivity to drugs and specifically for the endocytosis and turnover of the uric acid‐xanthine transporter UapA . A single arrestin‐like protein, ArtA , is essential for HulA Rsp 5 ‐dependent ubiquitination and endocytosis of UapA in response to ammonium or substrates. Mutational analysis showed that residues 545–563 of the UapA C ‐terminal region are required for efficient UapA endocytosis, whereas the N ‐terminal region (residues 2–123) and both PPxY motives are essential for ArtA function. We further show that ArtA undergoes HulA ‐dependent ubiquitination at residue Lys‐ 343 and that this modification is critical for UapA ubiquitination and endocytosis. Lastly, we show that ArtA is essential for vacuolar turnover of transporters specific for purines ( AzgA ) or l ‐proline ( PrnB ), but not for an aspartate/glutamate transporter ( AgtA ). Our results are discussed within the frame of recently proposed mechanisms on how arrestin‐like proteins are activated and recruited for ubiquitination of transporters in response to broad range signals, but also put the basis for understanding how arrestin‐like proteins, such as ArtA , regulate the turnover of a specific transporter in the presence of its substrates.