Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo

Inés Ibañez-Tallon, Hua Wen, Julie M. Miwa, Jie Xing, Ayse B. Tekinay, Fumihito Ono, Paul Brehm, Nathaniel Heintz

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The physiologies of cells depend on electrochemical signals carried by ion channels and receptors. Venomous animals produce an enormous variety of peptide toxins with high affinity for specific ion channels and receptors. The mammalian prototoxin lynx1 shares with α-bungarotoxin the ability to bind and modulate nicotinic receptors (nAChRs); however, lynx1 is tethered to the membrane via a GPI anchor. We show here that several classes of neurotoxins, including bungarotoxins and cobratoxins, retain their selective antagonistic properties when tethered to the membrane. Targeted elimination of nAChR function in zebrafish can be achieved with tethered α-bungarotoxin, silencing synaptic transmission without perturbing synapse formation. These studies harness the pharmacological properties of peptide toxins for use in genetic experiments. When combined with specific methods of cell and temporal expression, the extension of this approach to hundreds of naturally occurring peptide toxins opens a new landscape for cell-autonomous regulation of cellular physiology in vivo.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalNeuron
Volume43
Issue number3
DOIs
StatePublished - Aug 5 2004
Externally publishedYes

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Bungarotoxins
Ion Channels
Peptides
Cell Physiological Phenomena
Membranes
Neurotoxins
Nicotinic Receptors
Zebrafish
Synaptic Transmission
Synapses
Pharmacology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo. / Ibañez-Tallon, Inés; Wen, Hua; Miwa, Julie M.; Xing, Jie; Tekinay, Ayse B.; Ono, Fumihito; Brehm, Paul; Heintz, Nathaniel.

In: Neuron, Vol. 43, No. 3, 05.08.2004, p. 305-311.

Research output: Contribution to journalArticle

Ibañez-Tallon, Inés ; Wen, Hua ; Miwa, Julie M. ; Xing, Jie ; Tekinay, Ayse B. ; Ono, Fumihito ; Brehm, Paul ; Heintz, Nathaniel. / Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo. In: Neuron. 2004 ; Vol. 43, No. 3. pp. 305-311.
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