#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.
KIF1A Research
A kinesin-1 variant reveals motor-induced microtubule damage in cells
We commonly use the analogy of KIF1A as trucks carrying cargo down the long neuronal roads of microtubules. Mutations in kinesin motors can change the way the speed, reliability, and even the direction of cargo along the road. However, kinesin mutations don’t just impact the truck; just like roads experience wear and tear over time, microtubules may be damaged by motor protein movement, which can have large impacts on the long-term stability of cargo transport.
We commonly use the analogy of KIF1A as trucks carrying cargo down the long neuronal roads of microtubules. Mutations in kinesin motors can change the way the speed, reliability, and even the direction of cargo along the road. However, kinesin mutations don’t just impact the truck; just like roads experience wear and tear over time, microtubules may be damaged by motor protein movement, which can have large impacts on the long-term stability of cargo transport.
This week’s paper investigated a mutation in KIF5C, a kinesin-1 family member. This mutation resulted in KIF5C moving faster than normal while generating less force with each step. Surprisingly, the authors found that this form of KIF5C caused microtubules to bend, knot, and eventually break. While microtubules break and repair themselves under normal conditions, mutant KIF5C caused damage too drastic for repair processes to overcome. They directly compared this to a constitutively active KIF1A protein, which they found did not cause the same level of microtubule breakage.
Damage to a neuron’s cytoskeleton can have many negative consequences for cellular health, compounding the issues caused by primary motor dysfunction. While the particular KIF1A mutant studied here did not induce notable damage, there are many types of KIF1A mutations across the KAND community. Microtubule breakage may provide a valuable assay for assessing cellular health in kinesin mutations.
Rare Disease News
Upcoming Webinar: Deliver CRISPR to the Brain – A New Treatment Strategy for Mucopolysaccharidoses
In our April Community Call, we discussed the potential – and challenges – of gene editing therapies to treat neurological disorders like KAND. Chief among those challenges was the ability to deliver these therapies across the Blood Brain Barrier to affect central nervous system neurons. This is a common hurdle and an area where different disease research communities can compare notes to create the best possible solutions. On May 25th from 9am-10:30am EST, CRISPR News Medicine will be hosting a webinar where Dr. Guilherme Baldo discusses preclinical mouse research of intranasal CRISPR delivery as a mechanism of gene editing therapy for the brain.