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Updated: Jul 31, 2025

Isolation of Atrial Myocytes from Adult Mice
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Identification of a new Corin atrial natriuretic peptide-converting enzyme substrate: Agouti-signaling protein (ASIP)

Bryan T MacDonald1, Nadine H Elowe2, Colin W Garvie2

  • 1Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.

Biorxiv : the Preprint Server for Biology
|May 10, 2023
PubMed

Insights

Corin, an enzyme controlling blood pressure, also affects coat color by directly processing agouti-signaling protein (ASIP). This finding reveals a novel function for Corin in pigmentation, linked to ASIP regulation.

Area of Science:

  • Biochemistry
  • Genetics
  • Physiology

Background:

  • Corin is a transmembrane enzyme crucial for processing atrial natriuretic peptide (ANP), regulating blood pressure and electrolyte balance.
  • Loss-of-function mutations in Corin cause hypertension and are associated with lighter coat pigmentation across species.
  • The pigmentation phenotype is genetically linked to the Agouti locus, which encodes agouti-signaling protein (ASIP).

Approach:

  • Investigated the molecular mechanism linking Corin to pigmentation.
  • Utilized biochemical assays to determine the interaction between Corin and ASIP.
  • Analyzed the proteolytic activity of Corin on ASIP.

Key Points:

  • Agouti-signaling protein (ASIP) is identified as a direct proteolytic substrate of the Corin enzyme.
  • Corin directly cleaves ASIP, suggesting a novel enzymatic role beyond ANP processing.
  • This direct interaction provides a molecular basis for the observed correlation between Corin function and coat color.

Conclusions:

  • Corin's function extends to the direct processing of ASIP, a key regulator of pigmentation.
  • This discovery elucidates the conserved role of Corin in controlling both physiological (blood pressure) and pigmentary phenotypes.
  • Further research into Corin-ASIP interactions may offer insights into pigmentation disorders and related genetic traits.

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