A novel prohormone processing site in aplysia californica: The Leu-Leu rule

Amanda B. Hummon, He Qing Huang, Wayne P. Kelley, Jonathan V Sweedler

Research output: Contribution to journalArticlepeer-review


Neuropeptides are a complex set of signaling molecules produced through enzymatic cleavages from longer prohormone sequences. The most common cleavage sites in prohormones are basic amino acid residues; however, processing is observed at non-basic sites. Cleavage at Leu-Leu sequences has been observed in three Aplysia californica prohormones. To further investigate this unusual event, native and nonnative synthetic peptides containing Leu-Leu residues are incubated with homogenates of Aplysia californica ganglia and the resulting products monitored with MALDI MS. Cleavage near and between Leu-Leu residues is observed in the abdominal and buccal ganglia homogenates, confirming the presence of an unidentified peptidase. In addition, fractions from an HPLC separation of buccal ganglia homogenates also produce cleavages at Leu-Leu residues. Products resulting from cleavage at Leu-Leu sites are observed and are produced in larger amounts in acidic and neutral pH ranges, and cleavage is inhibited by the addition of EDTA, suggesting a metal is required for activity.

Original languageEnglish (US)
Pages (from-to)1398-1405
Number of pages8
JournalJournal of Neurochemistry
Issue number6
StatePublished - Sep 2002


  • Leucine-Leucine cleavages
  • Neuropeptides
  • Prohormone processing

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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