Tag Archives: G529R

More moonlighting

Well we used to think we understood what ion channels in the cell membrane did and how they worked. To a significant extent we do know how they conduct ions, permitting some and keeping others out in response to changes in membrane potential and neurotransmitters. It’s when they start doing other things that we begin to realize that we’re not in Kansas anymore.

Abnormal binding of one protein (filamin A) to one of the classic ion channels (the alpha7 nicotinic cholinergic receptor) may actually lead to a therapy for Alzheimer’s disease — for details please see — https://luysii.wordpress.com/2021/03/25/the-science-behind-cassava-sciences-sava/

The Kv3.3 voltage gating potassium channel is widely expressed in the brain.  Large amounts are found neurons concerned with sound, where firing rates are high.  Kv3.3 repolarizes them (and quickly) so they can fire again in response to high frequency stimuli (e.g. sound).  Kv3.3 is also found in the cerebellum and a mutation Glycine #529 –> Arginine is associated with a hereditary disease causing incoordination (type 13 spinocerebellar ataxia or SCA13 to be exact).

Amazingly the mutant conducts potassium ions quite normally.  The mutation (G529R) causes the channel not to bind to something called Arp2/3 with the result that actin (a muscle protein but found in just about every cell in the body) doesn’t form the network it usually does  at the synapse.  Synapses don’t work normally when this happens. 

Why abnormally functioning synapses isn’t lethal is anyone’s guess, as is why the mutation only affects the cerebellum.  So it’s another function of an ion channel, completely unrelated to its ability to conduct ions (e.g. moonlighting).