CELL-TYPE-SPECIFIC SORTING OF NEUROPEPTIDES - A MECHANISM TO MODULATEPEPTIDE COMPOSITION OF LARGE DENSE-CORE VESICLES

The CNS of Lymnaea stagnalis contains two populations of egg-laying ho rmone (ELH)-producing neurons that differ in size and topology. In typ e I neurons, all peptides located C-terminally from the cleavage site Arg-Ser-Arg-Arg(180-183) are sorted into secretory large dense-core ve sicles (LDCV), whereas N-terminal-located peptides accumulate in a dis tinct type of vesicle, the large electrondense granule (LEG). Via immu noelectron microscopy, we now show that the second population of ELH-p roducing neurons, type II neurons, lack LEG and incorporate all proELH -derived peptides into LDCV. This finding provides the first example o f a cell type-specific sorting of neuropeptides into LDCV. Furthermore , we provide evidence that LEG are formed through a differential conde nsation process in the trans-Golgi network and that these bodies are u ltimately degraded. Analysis of the endoprotease composition of the tw o types of proELH-producing neurons suggests that the formation of LEG , and consequently the retention of N-terminal peptides from the secre tory pathway, requires the action of a furin-like protein.