Vasopressin-activated calcium-mobilizing (VACM-1)/cul5 is the least conserved member of a cullin protein family involved in the formation of E3-specific ligase complexes that are responsible for delivering the ubiquitin protein to their target substrate proteins selected for ubiquitin-dependent degradation. This chapter summarizes work to date that has focused on VACM-1/cul5's tissue-specific expression in vivo and on its potential role in the control of specific cellular signaling pathways in those structures. As mammalian cells may contain hundreds of E3 ligases, identification VACM-1/cul5 as a specific subunit of the system that is expressed in the endothelium and in collecting tubules, structures known for their control of cellular permeability, may have significant implications when designing studies to elucidate the mechanism of water conservation. For example, VACM-1/cul5 expression is affected by water deprivation in some tissues and there is a potential relationship between neddylated VACM-1/cul5 and aquaporins.
Keywords: Aquaporin; Cullin; Endothelium; Neddylation; Tissue expression; Ubiquitin–proteasome system; VACM-1; Vasopressin-activated calcium-mobilizing receptor; Water deprivation.