Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age.

Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Research Abstract Details 

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Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Abstract Text:

Ryan Dackor,Kim Fritz-Six,Oliver Smithies,Kathleen Caron,

RAMPs (receptor activity modifying proteins) impart remarkable effects on G protein-coupled receptor (GPCR) signaling. First identified through an interaction with the calcitonin receptor-like receptor (CLR), these single transmembrane proteins are now known to modulate the in vitro ligand binding affinity, trafficking, and second messenger pathways of numerous GPCRs. Consequently, the receptor-RAMP interface represents an attractive pharmacological target for the treatment of disease. Although the three known mammalian RAMPs differ in their sequences and tissue expression, results from in vitro biochemical and pharmacological studies suggest that they have overlapping effects on the GPCRs with which they interact. Therefore, to determine whether RAMP2 and RAMP3 have distinct functions in vivo, we generated mice with targeted deletions of either the RAMP2 or RAMP3 gene. Strikingly, we found that, although RAMP2 is required for survival, mice that lack RAMP3 appear normal until old age, at which point they have decreased weight. In addition, mice with reduced expression of RAMP2 (but not RAMP3) display remarkable subfertility. Thus, each gene has functions in vivo that cannot be accomplished by the other. Because RAMP2, RAMP3, and CLR transduce the signaling of the two potent vasodilators adrenomedullin and calcitonin gene-related peptide, we tested the effects of our genetic modifications on blood pressure, and no effects were detected. Nevertheless, our studies reveal that RAMP2 and RAMP3 have distinct physiological functions throughout embryogenesis, adulthood, and old age, and the mice we have generated provide novel genetic tools to further explore the utility of the receptor-RAMP interface as a pharmacological target.

Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Publishing Authors By Initials

R Dackor,K Fritz-Six,O Smithies,K Caron,

For similar proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled: receptors, calcitonin research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, g-protein-coupled: receptors, calcitonin research

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MEDLINE DATE:

Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 18094-9

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 30

MONTH: 04

YEAR: 2007

Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Keywords Mesh Terms:

KEYWORDS: Receptors, Calcitonin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. Information

Substance Name: Calcitonin Gene-Related Peptide

Registry Number: 83652-28-2

Grant and Affiliation Information for Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age.

AFFILIATION: Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL49277

ACRONYM: HL

MEDLINETA: J Biol Chem

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