CaltechAUTHORS
  A Caltech Library Service

The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo

Miwa, Julie M. and Stevens, Tanya R. and King, Sarah L. and Caldarone, Barbara J. and Ibanez-Tallon, Ines and Xiao, Cheng and Fitzsimonds, Reiko Maki and Pavlides, Constantine and Lester, Henry A. and Picciotto, Marina R. and Heintz, Nathaniel (2006) The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo. Neuron, 51 (5). pp. 587-600. ISSN 0896-6273. https://resolver.caltech.edu/CaltechAUTHORS:20200427-095213669

[img] PDF (Supplemental Experimental Procedures) - Supplemental Material
See Usage Policy.

183Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200427-095213669

Abstract

Nicotinic acetylcholine receptors (nAChRs) affect a wide array of biological processes, including learning and memory, attention, and addiction. lynx1, the founding member of a family of mammalian prototoxins, modulates nAChR function in vitro by altering agonist sensitivity and desensitization kinetics. Here we demonstrate, through the generation of lynx1 null mutant mice, that lynx1 modulates nAChR signaling in vivo. Its loss decreases the EC₅₀ for nicotine by ∼10-fold, decreases receptor desensitization, elevates intracellular calcium levels in response to nicotine, and enhances synaptic efficacy. lynx1 null mutant mice exhibit enhanced performance in specific tests of learning and memory. Consistent with reports that mutations resulting in hyperactivation of nAChRs can lead to neurodegeneration, aging lynx1 null mutant mice exhibit a vacuolating degeneration that is exacerbated by nicotine and ameliorated by null mutations in nAChRs. We conclude that lynx1 functions as an allosteric modulator of nAChR function in vivo, balancing neuronal activity and survival in the CNS.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.neuron.2006.07.025DOIArticle
ORCID:
AuthorORCID
Xiao, Cheng0000-0001-9649-7450
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2006 Elsevier Inc. Received 21 December 2004, Revised 21 October 2005, Accepted 19 July 2006, Available online 6 September 2006. We wish to thank A.L. Beaudet for generously providing the α7 and β2 nAChR mutant mice used in these experiments. Special thanks to Dr. Andreas Walz, Dr. S. Selesnick, and Dr. P. Gutin. For helpful scientific discussions and/or technical support, thanks to C. Fletcher, R.A. Lester, A.B. Tekinay, R. Nashmi, A. Tapper, R. Pantoja, F. Moss, and B. Cohen and other members of HAL lab; B. Switzer of NSA, A. Kolar, S. Krueger, and A. Aslantas. Support for M.R.P., S.L.K., B.J.C., and T.R.S.: DA00436, DA15241, and AA15632; for J.M.M., NIH CA09673; for N.H., J.M.M., and I.I.-T., HHMI and NIH NIH R21 NS047751; for H.A.L. and C.X., DA-17279 and CA Tobacco-Related Disease Research Project.
Funders:
Funding AgencyGrant Number
NIHDA00436
NIHDA15241
NIHAA15632
NIHCA09673
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHR21 NS047751
NIHDA-17279
California Tobacco-Related Disease Research ProgramUNSPECIFIED
Subject Keywords:MOLNEURO; SYSNEURO
Issue or Number:5
Record Number:CaltechAUTHORS:20200427-095213669
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200427-095213669
Official Citation:Julie M. Miwa, Tanya R. Stevens, Sarah L. King, Barbara J. Caldarone, Ines Ibanez-Tallon, Cheng Xiao, Reiko Maki Fitzsimonds, Constantine Pavlides, Henry A. Lester, Marina R. Picciotto, Nathaniel Heintz, The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo, Neuron, Volume 51, Issue 5, 2006, Pages 587-600, ISSN 0896-6273, https://doi.org/10.1016/j.neuron.2006.07.025. (http://www.sciencedirect.com/science/article/pii/S0896627306005940)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102796
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:27 Apr 2020 18:00
Last Modified:27 Apr 2020 18:00

Repository Staff Only: item control page