Ubiquitination of aquaporin-2 in the kidney

Abstract

Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation.

Keywords: aquaporin 2; kidney tubules, collecting; ubiquitination; vasopressins.

Fig. 1

Aquaporin-2 (AQP2) trafficking and endocytosis. Short-term regulated trafficking of AQP2-expressing vesicles to the apical plasma membrane occurs in response to vasopressin stimulation. In contrast, ubiquitination is important for endocytosis and lysosomal degradation of AQP2 mainly in the multivescicular bodies (MVB). Ub, ubiquitin; P, phosphorylation; E3, Ub-protein ligase.

Fig. 2

Ubiquitin (Ub)-conjugation pathway. Activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). The E1 (Ub-activating enzyme) activates the C-terminus of Ub in an ATP-dependent manner, and both E2 (Ub-conjugating enzyme) and E3 (Ub-protein ligase) are involved in the attachment of Ub to a target protein (S) specifically through the ε-amino group of a lysine residue. (Modified from the previous study14)) Cys, cysteine; Lys, lysine; ATP, adenosine-5'-triphosphate; AMP, adenosine monophosphate; PPi, pyrophosphate; HECT, homologous to E6-associated protein C-terminus; RING, really interesting new gene.