World Library  
Flag as Inappropriate
Email this Article

Shaker gene

Article Id: WHEBN0003971465
Reproduction Date:

Title: Shaker gene  
Author: World Heritage Encyclopedia
Language: English
Subject: Kv1.1, Ion channel, Genetic disorders, GJB4, Q-type calcium channel
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

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
Entrez 3738
HUGO 6221
OMIM 176263
RefSeq NM_002232
UniProt P22001
Other data
Locus Chr. 1 p13.3

The shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster.[1][2][3][4] 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.

In Drosophila, the shaker gene is located on the X chromosome. The closest human homolog is KCNA3.[5]

Function

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.[7][8][9]

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]

Blockers

The ‘Shaker K’ channel is effected 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]

References

  1. ^ Salkoff L, Wyman R (1981). "Genetic modification of potassium channels in Drosophila Shaker mutants". Nature 293 (5829): 228–30.  
  2. ^ 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.  
  3. ^ 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.  
  4. ^ Lichtinghagen R, Stocker M, Wittka R, Boheim G, Stühmer W, Ferrus A, Pongs O (December 1990). "Drosophila melanogaster"Molecular basis of altered excitability in Shaker mutants of . EMBO J. 9 (13): 4399–407.  
  5. ^
  6. ^ MacKinnon R (March 1991). "Determination of the subunit stoichiometry of a voltage-activated potassium channel". Nature 350 (6315): 232–5.  
  7. ^ Schoppa NE, Sigworth FJ (February 1998). "Activation of shaker potassium channels. I. Characterization of voltage-dependent transitions". J. Gen. Physiol. 111 (2): 271–94.  
  8. ^ 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.  
  9. ^ 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.  
  10. ^ 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.  
  11. ^ a b c 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.  
  12. ^ 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.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.