The tip-E mutation of Drosophila decreases saxitoxin binding and interacts with other mutations affecting nerve membrane excitability.
A recessive temperature-sensitive paralytic mutation, tip-E, is associated with reduced binding of [3H]saxitoxin to voltage-sensitive sodium channels in membranes from adult Drosophila heads. There is a decrease of 30-40% in the number of [3H]saxitoxin-binding sites per mg protein (Bmax), but the dissociation constant (Kd) for [3H]saxitoxin binding is normal in the remaining population of binding sites. This decrease is not due to a general hypotrophy of neural tissue since the number of alpha-bungarotoxin binding sites is normal in tip-E mutants. Although saxitoxin binding is reduced in vitro, pharmacological experiments suggest that tip-E mutants have close to the wild-type number of sodium channels in vivo. This suggestion is supported by the observation that at permissive temperatures tip-E only marginally suppresses a mutation which causes enhanced membrane excitability. However, even at permissive temperatures tip-E interacts synergistically with mutations that decrease membrane excitability. In this case, the double mutants exhibit reduced viability and/or longevity. We postulate that either the structure of sodium channels or their microenvironment is altered in tip-E mutants resulting in an increased liability of binding sites in vitro.
F R
FR
Jackson
S D
SD
Wilson
L M
LM
Hall
D029845:Amphibian Proteins; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D009043:Motor Activity; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D012530:Saxitoxin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D029845:Amphibian Proteins; D002352:Carrier Proteins; D007473:Ion Channels; C027525:saxitoxin-binding protein, Rana catesbeiana; D012530:Saxitoxin; D012964:Sodium