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Stress Conditions Promote Yeast Gap1 Permease Ubiquitylation and Downregulation via the Arrestin-like Bul and Aly Proteins.

par Crapeau, Myriam ;Merhi, Ahmad ;André, Bruno
Référence The Journal of biological chemistry
Publication Publié, 2014-06

Article révisé par les pairs

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Résumé :

Gap1, the yeast general amino acid permease, is a convenient model for studying how the intracellular traffic of membrane transporters is regulated. Present at the plasma membrane under poor nitrogen supply conditions, it undergoes ubiquitylation, endocytosis, and degradation upon activation of the TORC1 kinase complex in response to an increase in internal amino acids. This downregulation is stimulated by TORC1-dependent phosphoinhibition of the Npr1 kinase, resulting in activation by dephosphorylation of the arrestin-like Bul1 and Bul2 adaptors recruiting the Rsp5 ubiquitin ligase to Gap1. We here report that Gap1 is also downregulated when cells are treated with the TORC1 inhibitor rapamycin or subjected to various stresses, and that a lack of the Tco89 subunit of TORC1 causes constitutive Gap1 downregulation. Both the Bul1 and Bul2 and the Aly1 and Aly2 arrestin-like adaptors of Rsp5 promote this downregulation without undergoing dephosphorylation. Furthermore, they act via C-terminal regions of Gap1 not involved in ubiquitylation in response to internal amino acids, whereas a Gap1 mutant altered in the N-terminal tail and resistant to ubiquitylation by internal amino acids is efficiently downregulated under stress via the Bul and Aly adaptors. While the Bul proteins mediate Gap1 ubiquitylation of two possible lysines, K9 and K16, the Aly proteins promote ubiquitylation of the K16 residue only. This stress-induced pathway of Gap1 downregulation targets other permeases as well, and likely allows cells facing adverse conditions to retrieve amino acids from permease degradation.