Receptor activity-modifying proteins (RAMPs) are a class of protein that interact with and modulate the activities of several Class B

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s including the receptors for

secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...

(CT),

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

, and

vasoactive intestinal peptide Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the ligan ...

(VIP). There are three distinct types of RAMPs in mammals (though more in fish), designated

RAMP1 Receptor activity modifying protein 1 is a protein that in humans is encoded by the ''RAMP1'' gene. The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity mod ...

RAMP2 Receptor activity modifying protein 2, also known as RAMP2, is a protein which in humans is encoded by the ''RAMP2'' gene. Function The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, calle ...

, and

RAMP3 Receptor activity modifying protein 3, also known as RAMP3, is a human gene. The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs) ...

, each encoded by a separate gene.

Function

Currently, the function of RAMPs is divided into classes of activities. When associated with the

Calcitonin receptor The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism. CT works by activating the G ...

(CTR) or Calcitonin receptor-like (CALCRL) (below), RAMPs can change the selectivity of the receptor for a specific hormone. In the cases of the other receptors mentioned, however, there is no evidence that they can do this, but instead function to regulate trafficking of receptors from the ER / golgi to the membrane. These functions appear to be ones where there is redundancy, as neither RAMP1 nor RAMP3

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

(KO) have grossly abnormal

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

s. The likelihood is that the phenotype of RAMP2 KO mice is more connected with the abolition of most

adrenomedullin Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the adrenal medulla: hence the name. In humans ADM is encoded ...

(AM) signalling than effects on trafficking of other receptors, as those mice are almost identical to AM KO mice and mice lacking the Calcitonin-like receptor which are unable to form either AM1 or AM-2 adrenomedullin receptors (CLR/RAMP2 and CLR/RAMP3 respectively).

Types

Association of RAMPs with either the CT or

CALCRL Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. Function The protein encoded by the CALCRL gene is a G protein-coupled rec ...

proteins forms 6 different receptors from the calcitonin receptor family:*

References

External links

* * Single-pass transmembrane proteins {{protein-stub