|Chromosome||X: 17.8 - 17.98 Mb|
|potassium voltage-gated channel, shaker-related subfamily, member 3|
|Locus||Chr. 1 p13.3|
The shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster.1234 Under ether anesthesia, 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 their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs.
The Sh gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell. A working Shaker channel is voltage-dependent and 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 of ion channels are responsible for the repolarization of the cell.
The ‘Shaker K’ channel is a homo tetrameric protein 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.789
Recently, 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
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
- Salkoff L, Wyman R (1981). "Genetic modification of potassium channels in Drosophila Shaker mutants". Nature 293 (5829): 228–30. doi:10.1038/293228a0. PMID 6268986.
- 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. doi:10.1126/science.2441471. PMID 2441471.
- 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. doi:10.1038/331137a0. PMID 2448635.
- 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". EMBO J. 9 (13): 4399–407. PMC 552231. PMID 1702382.
- MacKinnon R (March 1991). "Determination of the subunit stoichiometry of a voltage-activated potassium channel". Nature 350 (6315): 232–5. doi:10.1038/350232a0. PMID 1706481.
- Schoppa NE, Sigworth FJ (February 1998). "Activation of shaker potassium channels. I. Characterization of voltage-dependent transitions". J. Gen. Physiol. 111 (2): 271–94. PMC 2222764. PMID 9450944.
- Schoppa NE, Sigworth FJ (February 1998). "Activation of Shaker potassium channels. II. Kinetics of the V2 mutant channel". J. Gen. Physiol. 111 (2): 295–311. PMC 2222768. PMID 9450945.
- Schoppa NE, Sigworth FJ (February 1998). "Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channels". J. Gen. Physiol. 111 (2): 313–42. PMC 2222769. PMID 9450946.
- 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. doi:10.1038/nature03486. PMID 15858564.
- Sack JT, Aldrich RW (July 2006). "Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway". J. Gen. Physiol. 128 (1): 119–32. doi:10.1085/jgp.200609492. PMC 2151558. PMID 16801385.
- 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 Sci. 17 (1): 107–18. doi:10.1110/ps.073122908. PMC 2144586. PMID 18042681.