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This article is part of the Research Topic Genetic techniques and circuit analysis


Front. Mol. Neurosci., 30 October 2009 | http://dx.doi.org/10.3389/neuro.02.021.2009

Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators

York College and The Graduate Center, The American Museum of Natural History, The City University of New York, New York, NY, USA
Max-Delbrück Center for Molecular Medicine, Berlin, Germany
Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specific receptors and ion channels using engineered modulators. A novel strategy, termed “tethered toxins”, was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins.Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be engineered, coupled with the increasing number of neuroactive venom toxins and ligand peptides being discovered, imply a multitude of potentially innovative applications for manipulating neuronal circuits and tissue-specifi c cell networks, including treatment of disorders caused by malfunction of receptors and ion channels.
tethered-toxins, cell-surface modulators, lynx1, receptors, ion channels
Holford M, Auer S, Laqua M and Ibañez-Tallon I (2009). Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators. Front. Mol. Neurosci. 2:21. doi: 10.3389/neuro.02.021.2009
03 July 2009;
 Paper pending published:
17 July 2009;
10 October 2009;
 Published online:
30 October 2009.

Edited by:

William Wisden, Imperial College, UK

Reviewed by:

Peer Wulff, University of Aberdeen, UK
Sheriar Hormuzdi, University of Dundee, UK
William Wisden, Imperial College, UK
© 2009 Holford, Auer, Laqua and Ibañez-Tallon. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Ines Ibañez-Tallon, Molecular Neurobiology Group, Max-Delbrück Center for Molecular Medicine, Helmoltz Gemeinschaft, Robert-Rössle Str. 10, Berlin-Buch, Berlin 13125, Germany.e-mail: ibanezi@mdc-berlin.de