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Precursor structure, expression, and tissue distribution of human guanylin
F J de Sauvage1, S Keshav, W J Kuang
1Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Summary
Guanylin, a peptide hormone, activates the STaR receptor in the intestine, playing a role in regulating intestinal fluid secretion. This discovery identifies a key endogenous activator for this important biological pathway.
Area of Science:
- Gastroenterology
- Molecular Biology
- Endocrinology
Background:
- Heat-stable enterotoxins (STa) from Escherichia coli induce diarrhea by activating the intestine-specific receptor-guanylyl cyclase STaR.
- Guanylin, a 15-amino acid peptide from rat jejunum, was previously proposed as a potential endogenous activator of STaR.
Purpose of the Study:
- To clone and characterize human and mouse cDNAs encoding guanylin precursors.
- To confirm guanylin as an endogenous activator of the STaR receptor.
Main Methods:
- Cloning and expression of human and mouse cDNAs.
- Purification and functional characterization of guanylin.
- Northern blot and in situ hybridization for mRNA expression analysis.
Main Results:
- Human and mouse cDNAs encoding guanylin precursors were identified.
- Processed guanylin, derived from proguanylin, binds to and activates STaR.
- Guanylin mRNA is highly expressed in the intestine, specifically in Paneth cells.
Conclusions:
- Guanylin is an endogenous activator of the STaR receptor.
- This finding elucidates a novel pathway in intestinal fluid regulation.