Regulation of P4-ATPases

P4-ATPases belong to a family of cation-transporting proteins, the P-type ATPases, that are involved in relevant physiological functions, such as the generation of electrochemical gradients across membranes or cell detoxification. In accordance to their relevance, P-type ATPases are subjected to several regulatory mechanisms. For instance, they all seem to have autoinhibitory domains located at the N- and/or C-terminal ends of the polypeptide. However, very little is known about the factors that regulate P4-ATPase activity.

 

Many P4-ATPases interact with members of the Cdc50 protein family, that act as beta subunits involved in exit from the endoplasmic reticulum and probably also in the lipid translocation activity. In yeast, the plasma membrane P4-ATPases Dnf1p and Dnf2p are known to be regulated by phosphorylation by specific kinases. In the yeast trans-Golgi network, the activity of another P4-ATPase, Drs2p is modulated by its interaction with lipids and elements of the vesiculation machinery.

 

Are these mechanisms common for other P4-ATPases from higher eukaryotes? Which are the amino acid residues involved in the regulation? Do P4-ATPases also contain autoinhibitory domains?

 

 

 

 

 

 

 

Figure 1: Schematic representation of a P4-ATPase showing the possible regulatory mechanisms, including the interaction with a beta subunit from the Cdc50 family of proteins. The arrow indicates the direction of lipid translocation.