Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1.
We previously identified lynx1 as a neuronal membrane molecule related to snake alpha-neurotoxins able to modulate nAChRs. Here, we show that lynx1 colocalizes with nAChRs on CNS neurons and physically associates with nAChRs. Single-channel recordings show that lynx1 promotes the largest of three current amplitudes elicited by ACh through alpha(4)beta(2) nAChRs and that lynx1 enhances desensitization. Macroscopic recordings quantify the enhancement of desensitization onset by lynx1 and further show that it slows recovery from desensitization and increases the EC(50). These experiments establish that direct interaction of lynx1 with nAChRs can result in a novel type of functional modulation and suggest that prototoxins may play important roles in vivo by modulating functional properties of their cognate CNS receptors.
Ibañez-Tallon
Inés
I
Laboratory of Molecular Biology, Howard Hughes Medical Institute, New York, NY 10021, USA.
Miwa
Julie M
JM
Wang
Hai Long
HL
Adams
Niels C
NC
Crabtree
Gregg W
GW
Sine
Steven M
SM
Heintz
Nathaniel
N
D000109:Acetylcholine / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014665:Vasodilator Agents; D014982:Xenopus laevis / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D058851:GPI-Linked Proteins; C485626:LYNX1 protein, human; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D014665:Vasodilator Agents; D000109:Acetylcholine