Shaker (gene)
| Shaker | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | Sh | ||||||
| Entrez | 32780 | ||||||
| RefSeq (mRNA) | NM_167596 | ||||||
| UniProt | P08510 | ||||||
| Other data | |||||||
| Chromosome | X: 17.8 - 17.98 Mb | ||||||
| |||||||
| potassium voltage-gated channel, shaker-related subfamily, member 3 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | KCNA3 | ||||||
| NCBI gene | 3738 | ||||||
| HGNC | 6221 | ||||||
| OMIM | 176263 | ||||||
| RefSeq | NM_002232 | ||||||
| UniProt | P22001 | ||||||
| Other data | |||||||
| Locus | Chr. 1p13.3 | ||||||
| |||||||
Theshaker (Sh)gene,whenmutated,causes a variety of atypical behaviors in the fruit fly,Drosophila melanogaster.[1][2][3][4]Underetheranesthesia,the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in theirlarvae,the repetitive firing ofaction potentialsas well as prolonged exposure toneurotransmittersatneuromuscular junctionsoccurs.
InDrosophila,the shaker gene is located on the X chromosome. The closest human homolog isKCNA3.[5]
Function
[edit]TheShgene plays a part in the operation ofpotassium ion channels,which areintegral membrane proteinsand are essential to the correct functioning of the cell. A working shaker channel isvoltage-dependentand has four subunits, which form a pore through which ions flow, carrying type-A potassium current (IA). A mutation in the Sh gene reduces the conductance of charge across the neuron since the channels do not work, causing the severe phenotypical aberrations mentioned above. These types ofion channelsare responsible for therepolarizationof the cell.
Theshaker Kchannel is a homotetramericprotein complex.[6]When confronted with a stimulus, the tetramers undergo conformational changes; some of these changes are cooperative. The final step involved in the opening of the channel is highly synchronized.[7][8][9]
The shaker gene has also been identified as a gene that helps determine an organism's amount of sleep. The phenotype of the flies that need less sleep is called minisleep (mns).[10]
Blockers
[edit]Theshaker Kchannel is affected by various toxins, which effectively slow the opening of the channel, or reversibly block its functioning.[11][12]
Toxins that affect the shaker K channel include:
BrMT can be seen working in the K channel to prevent the early activation of the channel – before the cooperation has begun.[11]Though its exact mechanism remains unknown, it is expected to work by forcing a conformational change in the pore domain of the channel. This part of the channel is expected to be altered instead of the voltage-sensing domain because of its connections to other subunits. When the conformational change is enacted, the BrMT sites on adjacent subunits are also affected, resulting in a widespread delayed activation of the K channel.[11]
See also
[edit]References
[edit]- ^Salkoff L, Wyman R (1981). "Genetic modification of potassium channels in Drosophila Shaker mutants".Nature.293(5829): 228–30.Bibcode:1981Natur.293..228S.doi:10.1038/293228a0.PMID6268986.S2CID4342210.
- ^Tempel BL, Papazian DM, Schwarz TL, Jan YN, Jan LY (August 1987). "Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila".Science.237(4816): 770–5.Bibcode:1987Sci...237..770T.doi:10.1126/science.2441471.PMID2441471.
- ^Schwarz TL, Tempel BL, Papazian DM, Jan YN, Jan LY (January 1988). "Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila".Nature.331(6152): 137–42.Bibcode:1988Natur.331..137S.doi:10.1038/331137a0.PMID2448635.S2CID4245558.
- ^Lichtinghagen R, Stocker M, Wittka R, Boheim G, Stühmer W, Ferrus A, Pongs O (December 1990)."Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster".The EMBO Journal.9(13): 4399–407.doi:10.1002/j.1460-2075.1990.tb07890.x.PMC552231.PMID1702382.
- ^HomoloGene:20513
- ^MacKinnon R (March 1991). "Determination of the subunit stoichiometry of a voltage-activated potassium channel".Nature.350(6315): 232–5.Bibcode:1991Natur.350..232M.doi:10.1038/350232a0.PMID1706481.S2CID4246808.
- ^Schoppa NE, Sigworth FJ (February 1998)."Activation of shaker potassium channels. I. Characterization of voltage-dependent transitions".The Journal of General Physiology.111(2): 271–94.doi:10.1085/jgp.111.2.271.PMC2222764.PMID9450944.
- ^Schoppa NE, Sigworth FJ (February 1998)."Activation of Shaker potassium channels. II. Kinetics of the V2 mutant channel".The Journal of General Physiology.111(2): 295–311.doi:10.1085/jgp.111.2.295.PMC2222768.PMID9450945.
- ^Schoppa NE, Sigworth FJ (February 1998)."Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels".The Journal of General Physiology.111(2): 313–42.doi:10.1085/jgp.111.2.313.PMC2222769.PMID9450946.
- ^Cirelli C, Bushey D, Hill S, Huber R, Kreber R, Ganetzky B, Tononi G (April 2005). "Reduced sleep in Drosophila Shaker mutants".Nature.434(7037): 1087–92.Bibcode:2005Natur.434.1087C.doi:10.1038/nature03486.PMID15858564.S2CID4370944.
- ^abcSack JT, Aldrich RW (July 2006)."Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway".The Journal of General Physiology.128(1): 119–32.doi:10.1085/jgp.200609492.PMC2151558.PMID16801385.
- ^Pimentel C, M'Barek S, Visan V, Grissmer S, Sampieri F, Sabatier JM, Darbon H, Fajloun Z (January 2008)."Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins".Protein Science.17(1): 107–18.doi:10.1110/ps.073122908.PMC2144586.PMID18042681.