The ''shaker (Sh)'' gene, when

mutated In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral rep ...

, causes a variety of atypical behaviors in the fruit fly, ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

''. Under

ether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R� ...

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

, 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

larva A larva (; : larvae ) is a distinct juvenile form many animals undergo before metamorphosis into their next life stage. Animals with indirect development such as insects, some arachnids, amphibians, or cnidarians typically have a larval phase ...

e, the repetitive firing of

action potentials An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. ...

as well as prolonged exposure to

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...

neuromuscular junctions A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

occurs. In ''Drosophila'', the shaker gene is located on the X chromosome. The closest human homolog is

KCNA3 Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the ''KCNA3'' gene. Potassium channels represent the most complex class of voltage-gated ion channels f ...

Function

The ''Sh'' gene plays a part in the operation of potassium ion channels, which are

integral membrane proteins An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs com ...

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 Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...

are responsible for the

repolarization In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarizat ...

of the cell. The ''shaker K'' channel is a homo

tetramer A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...

ic protein complex. 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. 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).

Blockers

The ''shaker K'' channel is affected by various toxins, which effectively slow the opening of the channel, or reversibly block its functioning. Toxins that affect the shaker K channel include: * Agitoxin * Charybdotoxin * Iberiotoxin *

Pandinotoxin Pandinotoxins are toxins from the venom of the emperor scorpion '' Pandinus imperator''. They are selective blockers of voltage-gated potassium channels Sources The source for the pandinotoxins is the venom of the scorpion '' Pandinus imperato ...

* 6-bromo-2-mercaptotryptamine (BrMT) BrMT can be seen working in the K channel to prevent the early activation of the channel – before the cooperation has begun. 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.

References

{{Ion channels, g3 Drosophila melanogaster genes Genetic diseases and disorders Ion channels

Function

Blockers

See also

References