Novel excitatory Conus peptides define a new conotoxin superfamily.
A new class of Conus peptides, the I-superfamily of conotoxins, has been characterized using biochemical, electrophysiological and molecular genetic methods. Peptides in this superfamily have a novel pattern of eight Cys residues. Five peptides that elicited excitatory symptomatology, r11a, r11b, r11c, r11d and r11e, were purified from Conus radiatus venom; four were tested on amphibian peripheral axons and shown to elicit repetitive action potentials, consistent with being members of the 'lightning-strike cabal' of toxins that effect instant immobilization of fish prey. A parallel analysis of Conus cDNA clones revealed a new class of conotoxin genes that was particularly enriched (with 18 identified paralogues) in a Conus radiatus venom duct library; several C. radiatus clones encoded the excitatory peptides directly characterized from venom. The remarkable diversity of related I-superfamily peptides within a single Conus species is unprecedented. When combined with the excitatory effects observed on peripheral circuitry, this unexpected diversity suggests a corresponding molecular complexity of the targeted signaling components in peripheral axons; the I-conotoxin superfamily should provide a rich lode of pharmacological tools for dissecting and understanding these. Thus, the I-superfamily conotoxins promise to provide a significant new technology platform for dissecting the molecular components of axons.
Jimenez
Elsie C
EC
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Shetty
Reshma P
RP
Lirazan
Marcelina
M
Rivier
Jean
J
Walker
Craig
C
Abogadie
Fe C
FC
Yoshikami
Doju
D
Cruz
Lourdes J
LJ
Olivera
Baldomero M
BM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001681:Biological Assay; D020916:Conotoxins / Q000235:genetics* / Q000302:isolation & purification* / Q000494:pharmacology; D004594:Electrophysiology; D015723:Gene Library; D006054:Goldfish; D066298:In Vitro Techniques; D051379:Mice; D008978:Mollusk Venoms / Q000737:chemistry; D005810:Multigene Family; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009498:Neurotoxins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification* / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects / Q000502:physiology; D011894:Rana pipiens; D020539:Sequence Analysis, Protein
D020916:Conotoxins; D008978:Mollusk Venoms; D009498:Neurotoxins; D010455:Peptides