Cell type-specific sorting of neuropeptides: a mechanism to modulate peptide composition of large dense-core vesicles

J Neurosci. 1996 Dec 15;16(24):7930-40. doi: 10.1523/JNEUROSCI.16-24-07930.1996.

Abstract

The CNS of Lymnaea stagnalis contains two populations of egg-laying hormone (ELH)-producing neurons that differ in size and topology. In type I neurons, all peptides located C-terminally from the cleavage site Arg-Ser-Arg-Arg180-183 are sorted into secretory large dense-core vesicles (LDCV), whereas N-terminal-located peptides accumulate in a distinct type of vesicle, the large electrondense granule (LEG). Via immunoelectron microscopy, we now show that the second population of ELH-producing neurons, type II neurons, lack LEG and incorporate all proELH-derived peptides into LDCV. This finding provides the first example of a cell type-specific sorting of neuropeptides into LDCV. Furthermore, we provide evidence that LEG are formed through a differential condensation process in the trans-Golgi network and that these bodies are ultimately degraded. Analysis of the endoprotease composition of the two types of proELH-producing neurons suggests that the formation of LEG, and consequently the retention of N-terminal peptides from the secretory pathway, requires the action of a furin-like protein.

MeSH terms

  • Animals
  • Furin
  • Invertebrate Hormones / chemistry
  • Invertebrate Hormones / metabolism*
  • Lymnaea
  • Microscopy, Immunoelectron
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Neuropeptides / metabolism*
  • Peptide Fragments / metabolism
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism
  • RNA, Messenger / metabolism
  • Subtilisins / genetics

Substances

  • Invertebrate Hormones
  • Neuropeptides
  • Peptide Fragments
  • Protein Precursors
  • RNA, Messenger
  • egg-laying hormone, Mollusca
  • Subtilisins
  • Furin