Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo.
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 alpha-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 alpha-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.
Howard Hughes Medical Institute, Laboratory of Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Inés
I
Ibañez-Tallon
Hua
H
Wen
Julie M
JM
Miwa
Jie
J
Xing
Ayse B
AB
Tekinay
Fumihito
F
Ono
Paul
P
Brehm
Nathaniel
N
Heintz
D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus; D015027:Zebrafish
D002038:Bungarotoxins; D007473:Ion Channels; D009498:Neurotoxins; D010455:Peptides; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins