Abstract

Neuronal nicotinic acetylcholine receptors (AChRs) will be studied using stably transfected QT-6 quail cell lines to express epitope-tagged chick neuronal AChR gene constructs under inducible promoters. a7 AChRs will be given special emphasis because of their unusual properties (they function as homomers, have high calcium permeability and are located extrasynaptically in ciliary ganglia). Also to be studied are combinations of a3, b4, a5 + b2 subunits (because AChRs of these types are found postsynaptically in ciliary ganglia). The cell lines will be used to analyze subunit interactions, assembly pathways, and functional properties. Surface AChRs will be quantitated using toxins and mAbs to the epitope tags. Function will be assayed by whole cell patch clamp recording. Assembly intermediates will be identified by pulse labeling and immune precipitation. Subunit composition will be analyzed by immunoprecipitation and immunoblot analysis using mAbs to subunits and tags. Distribution within the cells will be evaluated by confocal microscopy. Neuronal cell lines which express a7 will also be used for comparison. These studies should reveal important aspects of the cell and molecular biology of neuronal nicotinic receptors and are relevant to the role of nicotinic AChRs in nicotine addiction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035469-03
Application #
2669093
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Kitt, Cheryl A
Project Start
1996-05-01
Project End
2001-02-28
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Halff, Andrew W; Gómez-Varela, David; John, Danielle et al. (2014) A novel mechanism for nicotinic potentiation of glutamatergic synapses. J Neurosci 34:2051-64
Wang, Xulong; Lippi, Giordano; Carlson, David M et al. (2013) Activation of ?7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses. J Neurochem 127:632-43
Lozada, Adrian F; Wang, Xulong; Gounko, Natalia V et al. (2012) Glutamatergic synapse formation is promoted by ?7-containing nicotinic acetylcholine receptors. J Neurosci 32:7651-61
Lozada, Adrian F; Wang, Xulong; Gounko, Natalia V et al. (2012) Induction of dendritic spines by ?2-containing nicotinic receptors. J Neurosci 32:8391-400
Gómez-Varela, David; Schmidt, Manuela; Schoellerman, Jeff et al. (2012) PMCA2 via PSD-95 controls calcium signaling by ?7-containing nicotinic acetylcholine receptors on aspiny interneurons. J Neurosci 32:6894-905
Campbell, Nolan R; Fernandes, Catarina C; John, Danielle et al. (2011) Nicotinic control of adult-born neuron fate. Biochem Pharmacol 82:820-7
Berg, Darwin K (2011) Timing is everything, even for cholinergic control. Neuron 71:6-8
Fernandes, Catarina C; Berg, Darwin K; Gomez-Varela, David (2010) Lateral mobility of nicotinic acetylcholine receptors on neurons is determined by receptor composition, local domain, and cell type. J Neurosci 30:8841-51
Nai, Qiang; Wang, Xiaoyun; Jin, Ying et al. (2010) Ciliary neurotrophic factor enhances nicotinic synaptic transmission in sympathetic neurons. J Neurosci Res 88:887-95
Campbell, Nolan R; Fernandes, Catarina C; Halff, Andrew W et al. (2010) Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus. J Neurosci 30:8734-44

Showing the most recent 10 out of 58 publications