Cell type-specific sorting of neuropeptides: a mechanism to modulate peptide composition of large dense-core vesicles.
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.
Klumperman
J
J
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Faculty of Biology, 1081 HV Amsterdam, The Netherlands.
Spijker
S
S
van Minnen
J
J
Sharp-Baker
H
H
Smit
A B
AB
Geraerts
W P
WP
D000818:Animals; D045683:Furin; D007447:Invertebrate Hormones / Q000737:chemistry / Q000378:metabolism*; D008195:Lymnaea; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics
D007447:Invertebrate Hormones; D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C026880:egg-laying hormone, Mollusca; D013381:Subtilisins; D045683:Furin