Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila.
To investigate the possibility that kinesin transports vesicles bearing proteins essential for ion channel activity, the effects of kinesin (Khc) and ion channel mutations were compared in Drosophila using established tests. Our results show that Khc mutations produce defects and genetic interactions characteristic of paralytic (para) and maleless (mle) mutations that cause reduced expression or function of the alpha-subunit of voltage-gated sodium channels. Like para and mle mutations, Khc mutations cause temperature-sensitive (TS) paralysis. When combined with para or mle mutations, Khe mutations cause synthetic lethality and a synergistic enhancement of TS-paralysis. Furthermore, Khc: mutations suppress Shaker and ether-a-go-go mutations that disrupt potassium channel activity. In light of previous physiological tests that show that Khc mutations inhibit compound action potential propagation in segmental nerves, these data indicate that kinesin activity is required for normal inward sodium currents during neuronal action potentials. Tests for phenotypic similarities and genetic interactions between kinesin and sodium/potassium ATPse mutations suggest that impaired kinesin function does not affect the driving force on sodium ions. We hypothesize that a loss of kinesin function inhibits the anterograde axonal transport of vesicles bearing sodium channels.
Hurd
D D
DD
Department of Biology, Indiana University, bloomington 47405, USA.
Stern
M
M
Saxton
W M
WM
D000818:Animals; D001370:Axonal Transport / Q000235:genetics*; D003433:Crosses, Genetic; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017344:Genes, Insect; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010243:Paralysis / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013696:Temperature
D015221:Potassium Channels; D015222:Sodium Channels; D016547:Kinesins; D000254:Sodium-Potassium-Exchanging ATPase