Liver retinol transporter and receptor for serum retinol-binding protein (RBP4)

Area of Science:

• Molecular Biology
• Endocrinology
• Nutritional Science

Background:

• Vitamin A (retinol) transport involves serum retinol-binding protein (RBP4), crucial for its delivery to tissues.
• While RBP4 binding sites exist in the liver, specific receptors mediating retinol uptake have remained elusive.
• The known RBP4 receptor, Stra6, is absent in the liver, necessitating the search for alternative mechanisms.

Purpose of the Study:

• To identify novel receptors involved in RBP4-mediated retinol transport, particularly in the liver.
• To characterize the function and expression pattern of a newly discovered RBP4 receptor, RBPR2.

Main Methods:

• Discovery and characterization of RBPR2, a novel retinol transporter.
• Assessment of RBPR2 expression in liver, intestine, and adipose tissue.
• Functional studies in cultured cells to evaluate RBP4 binding and retinol transport.
• In vivo correlation of RBPR2 expression with liver retinol stores.

Main Results:

• Identification of RBPR2, a novel retinol transporter structurally related to Stra6 and conserved across vertebrates.
• RBPR2 expression is prominent in the liver and intestine, and induced in adipose tissue of obese mice.
• RBPR2 confers high-affinity RBP4 binding and retinol transport in cultured cells; its knockdown impairs these processes.
• RBPR2 expression is downregulated by retinol and retinoic acid and inversely correlates with liver retinol levels.

Conclusions:

• RBPR2 is a novel retinol transporter that plays a significant role in regulating retinol homeostasis.
• Its expression in the liver and adipose tissue suggests a role in mediating metabolic functions of RBP4.
• RBPR2 represents a potential new target for understanding and managing vitamin A metabolism.