MOLLUSCAN SUBTILISIN-RELATED ENDOPROTEASES INVOLVED IN THE ACTIVATION OF PROHORMONES AND PROPROTEINS IN THE SECRETORY PATHWAY

Gregg T. Nagle, Susan L. Knock, Walter R.A. Van Heumen, Alexander Kurosky

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Neuropeptides and pcptide hormones are synthesized as part of larger precursor proteins that are processed post-translationally by subtilisin-related prohormone convertases (PCs), frequently at multiple basic sites, to generate biologically active peptides. The neuroendocrine bag cells and exocrine atrial gland cells of Aplysia californica are model peptidergic cells that provide a unique opportunity to examine the processing and differential sorting of a family of egg-laying hormone (ELH)-related polyprotein precursors. Bag cell neurons synthesize and initially cleave the ELH prohormone at a unique tetrabasic site to generate NH. 2-terminal and COOH-terminal intermediates that are sorted to distinct vesicle classes in the trans-Golgi. The processing intermediates subsequently undergo an ordered series of cleavage steps to generate multiple products, including ELH. The atrial gland synthesizes and post-translationally processes large quantities of four ELH-related precursors to liberate multiple products, including ELH-related peptides. Four members of a family of Aplysia subtilisin-related endoproteases that are expressed in bag cell neurons or atrial gland cells have been cloned, and two of these enzymes are capable of correctly cleaving the ELH prohormone. The predicted primary structures of the preproendoproteases suggest that they undergo protcolytic cleavage at the consensus sequence Arg-Xaa-(Lys/Arg)-Arg prior to enzyme activation.

Original languageEnglish (US)
Pages (from-to)439-450
Number of pages12
JournalNetherlands Journal of Zoology
Volume44
Issue number3-4
DOIs
StatePublished - Jan 1 1993

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Keywords

  • Aplysia californica
  • Atrial gland
  • Bag cells
  • Prohormone convertases

ASJC Scopus subject areas

  • Animal Science and Zoology

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