Distinct modulating effects of TipE-homologs 2-4 on Drosophila sodium channel splice variants.
The Drosophila melanogaster TipE protein is thought to be an insect sodium channel auxiliary subunit functionally analogous to the β subunits of mammalian sodium channels. Besides TipE, four TipE-homologous proteins (TEH1-4) have been identified. It has been reported that TipE and TEH1 have both common and distinct effects on the gating properties of splice variants of the Drosophila sodium channel, DmNav. However, limited information is available on the effects of TEH2, TEH3 and TEH4 on the function of DmNav channel variants. In this study, we found that TEH2 increased the amplitude of peak current, but did not alter the gating properties of three examined DmNav splice variants expressed in Xenopus oocytes. In contrast, TEH4 had no effect on peak current, yet altered the gating properties of all three channel variants. Furthermore, TEH4 enhanced persistent current and slowed sodium current decay. The effects of TEH3 on DmNav variants are similar to those of TEH4, but the data were collected from a small portion of oocytes because co-expression of TEH3 with DmNav variants generated a large leak current in the majority of oocytes examined. In addition, TEH3 and TEH4 enhanced the expression of endogenous currents in oocytes. Taken together, our results reveal distinct roles of TEH proteins in modulating the function of sodium channels and suggest that TEH proteins might provide an important layer of regulation of membrane excitability in vivo. Our results also raise an intriguing possibility of TEH3/TEH4 as auxiliary subunits of other voltage-gated ion channels besides sodium channels.
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA.
Lingxin
L
Wang
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA.
Yuzhe
Y
Du
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA.
Yoshiko
Y
Nomura
Department of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, MI 48823, USA. Electronic address: dongk@cns.msu.edu.
Ke
K
Dong
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*; D014981:Xenopus
D029721:Drosophila Proteins; D008565:Membrane Proteins; C000603757:TEH2 protein, Drosophila; C000603758:TEH3 protein, Drosophila; C000603759:TEH4 protein, Drosophila; C095833:TipE protein, Drosophila; D061566:Voltage-Gated Sodium Channels
Auxiliary subunit; Drosophila melanogaster; Sodium channels; TipE; TipE-homologous proteins