Mammalian multidrug-resistance proteins (MRPs)

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• The human ABC superfamily includes nine proteins known as multidrug-resistance proteins (MRPs).
• These transporters exhibit structural variations, including 'short' and 'long' forms, influencing their function.
• While some MRPs transport drugs and endogenous compounds, others have unknown in vivo substrates.

Purpose of the Study:

• To elucidate the diverse roles and substrate specificities of the nine MRP/ABCC transporters.
• To highlight the structural differences and tissue distribution patterns of these transporters.
• To underscore the importance of MRPs in cellular transport and physiological processes.

Main Methods:

• Comparative analysis of MRP/ABCC transporter structures.
• Review of studies on substrate specificity and tissue distribution.
• Investigation of gene-knockout mouse models to identify in vivo substrates.

Main Results:

• MRP/ABCC transporters exhibit distinct structural domains ('short' vs. 'long' forms).
• Transport substrates include exogenous drug metabolites and endogenous signaling molecules.
• Tissue distribution and membrane localization vary, contributing to unique functions.
• In vivo substrates for MRP5, MRP7, ABCC6, and ABCC12 remain largely unidentified.

Conclusions:

• Structural and functional diversity among MRP/ABCC transporters dictates their specific roles.
• Understanding MRP substrate specificity is crucial for pharmacology and physiology.
• Further research is needed to fully characterize the in vivo functions of all nine MRPs.