Characterization of carboxypeptidase A6, an extracellular matrix peptidase

Peter J. Lyons, Myrasol B. Callaway, Lloyd D. Fricker

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Carboxypeptidase A6 (CPA6) is a member of the M14 metallocarboxypeptidase family that is highly expressed in the adult mouse olfactory bulb and broadly expressed in embryonic brain and other tissues. A disruption in the human CPA6 gene is linked to Duane syndrome, a defect in the abducens nerve/lateral rectus muscle connection. In this study the cellular distribution, processing, and substrate specificity of human CPA6 were investigated. The 50-kDa pro-CPA6 is routed through the constitutive secretory pathway, processed by furin or a furin-like enzyme into the 37-kDa active form, and secreted into the extracellular matrix. CPA6 cleaves the C-terminal residue from a range of substrates, including small synthetic substrates, larger peptides, and proteins. CPA6 has a preference for large hydrophobic C-terminal amino acids as well as histidine. Peptides with a penultimate glycine or proline are very poorly cleaved. Several neuropeptides were found to be processed by CPA6, including Met- and Leu-enkephalin, angiotensin I, and neurotensin. Whereas CPA6 converts enkephalin and neurotensin into forms known to be inactive toward their receptors, CPA6 converts inactive angiotensin I into the biologically active angiotensin II. Taken together, these data suggest a role for CPA6 in the regulation of neuropeptides in the extracellular environment within the olfactory bulb and other parts of the brain.

Original languageEnglish (US)
Pages (from-to)7054-7063
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number11
DOIs
StatePublished - Mar 14 2008

Fingerprint

Carboxypeptidases
Extracellular Matrix
Peptide Hydrolases
Furin
Angiotensin I
Neurotensin
Olfactory Bulb
Neuropeptides
Brain
Substrates
Duane Retraction Syndrome
Abducens Nerve
Leucine Enkephalin
Methionine Enkephalin
Peptides
Enkephalins
Secretory Pathway
Substrate Specificity
Histidine
Proline

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Characterization of carboxypeptidase A6, an extracellular matrix peptidase. / Lyons, Peter J.; Callaway, Myrasol B.; Fricker, Lloyd D.

In: Journal of Biological Chemistry, Vol. 283, No. 11, 14.03.2008, p. 7054-7063.

Research output: Contribution to journalArticle

Lyons, Peter J. ; Callaway, Myrasol B. ; Fricker, Lloyd D. / Characterization of carboxypeptidase A6, an extracellular matrix peptidase. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 11. pp. 7054-7063.
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