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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
StatePublished - Oct 20 2000
Externally publishedYes

Fingerprint

Aplysia
Neuropeptides
Organism Cloning
Lyases
Enzymes
Enzyme Precursors
Central Nervous System
Peptides
Exons
Proprotein Convertase 2
Proprotein Convertase 1
Carboxypeptidase H
Furin
Endocrine System
Mollusca
Secretory Pathway
Invertebrates
Post Translational Protein Processing
Mixed Function Oxygenases
Ganglia

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Neuropeptide amidation : Cloning of a bifunctional α-amidating enzyme from Aplysia. / Fan, Xuemo; Spijker, Sabine; Akalal, David Benjamin G.; Nagle, Gregg Thomas.

In: Molecular Brain Research, Vol. 82, No. 1-2, 20.10.2000, p. 25-34.

Research output: Contribution to journalArticle

Fan, Xuemo ; Spijker, Sabine ; Akalal, David Benjamin G. ; Nagle, Gregg Thomas. / Neuropeptide amidation : Cloning of a bifunctional α-amidating enzyme from Aplysia. In: Molecular Brain Research. 2000 ; Vol. 82, No. 1-2. pp. 25-34.
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