Neuropeptide amidation: Cloning of a bifunctional α-amidating enzyme from Aplysia

Xuemo Fan, Sabine Spijker, David Benjamin G. Akalal, Gregg T. Nagle

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

One of the most common mechanisms of posttranslational modifications to generate biologically active (neuro)peptides is the process of peptide α-amidation. The only enzyme known to catalyze this important modification is peptidylglycine α-amidating monooxygenase (PAM): a (bifunctional) zymogen, giving rise to a monooxygenase (PHM) and a lyase (PAL). The highly peptidergic central nervous system and endocrine system of the marine mollusk Aplysia has homologs of various mammalian peptide processing enzymes, including furin, Afurin2, prohormone convertase 1 (PC1), PC2, carboxypeptidase E (CPE) and CPD. Previously, it has been shown that the abdominal ganglion of Aplysia, which contains ~800 peptidergic bag cell neurons, contains the highest specific α-amidating activity. We have identified and cloned multiple overlapping central nervous system and bag cell cDNAs that encode a predicted 748-residue protein that is a member of the PAM family. The protein sequence contains the contiguous sequence of the catalytic domains of PHM and PAL, clearly demonstrating the existence of bifunctional Aplysia PAM, the first invertebrate PAM zymogen with an organization similar to that in vertebrates. None of the characterized clones encoded the so-called exon A domain between the PHM and PAL domains. Furthermore, in a specific search by reverse transcription-polymerase chain reaction of RNA from multiple tissues we could only detect exon A-less transcripts. PAM expression was detected in the central nervous system, and in several endocrine and exocrine organs Aplysia PAM is a candidate prohormone processing enzyme that plays an important role in the processing of Aplysia prohormones in the secretory pathway. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalMolecular Brain Research
Volume82
Issue number1-2
DOIs
Publication statusPublished - Oct 20 2000
Externally publishedYes

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Keywords

  • Aplysia californica
  • Lyase
  • Monooxygenase
  • α-Amidating enzyme

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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