Distinct mechanisms produce functionally complementary actions of neuropeptides that are structurally related but derived from different precursors.
Many bioactive neuropeptides containing RFamide at their C terminus have been described in both invertebrates and vertebrates. To obtain insight into the functional logic of RFamide signaling, we investigate it here in the feeding system of Aplysia. We focus on the expression, localization, and actions of two families of RFamide peptides, the FRFamides and FMRFamide, in the central neuronal circuitry and the peripheral musculature that generate the feeding movements. We describe the cloning of the FRFamide precursor protein and show that the FRFamides and FMRFamide are derived from different precursors. We map the expression of the FRFamide and FMRFamide precursors in the feeding circuitry using in situ hybridization and immunostaining and confirm proteolytic processing of the FRFamide precursor by mass spectrometry. We show that the two precursors are expressed in different populations of sensory neurons in the feeding system. In a representative feeding muscle, we demonstrate the presence of both FRFamides and FMRFamide and their release, probably from the processes of the sensory neurons in the muscle. Both centrally and in the periphery, the FRFamides and FMRFamide act in distinct ways, apparently through distinct mechanisms, and nevertheless, from an overall functional perspective, their actions are complementary. Together, the FRFamides and FMRFamide convert feeding motor programs from ingestive to egestive and depress feeding muscle contractions. We conclude that these structurally related peptides, although derived from different precursors, expressed in different neurons, and acting through different mechanisms, remain related to each other in the functional roles that they play in the system.
Vilim
Ferdinand S
FS
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA. ferdinand.vilim@mssm.edu
Sasaki
Kosei
K
Rybak
Jurgen
J
Alexeeva
Vera
V
Cropper
Elizabeth C
EC
Jing
Jian
J
Orekhova
Irina V
IV
Brezina
Vladimir
V
Price
David
D
Romanova
Elena V
EV
Rubakhin
Stanislav S
SS
Hatcher
Nathan
N
Sweedler
Jonathan V
JV
Weiss
Klaudiusz R
KR
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D002478:Cells, Cultured; D019835:FMRFamide / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000502:physiology*; D011498:Protein Precursors / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009479:Neuropeptides; D011498:Protein Precursors; D019835:FMRFamide