Max Schelski
banner
maxschelski.bsky.social
Max Schelski
@maxschelski.bsky.social
Neuroscientist. Developing mathematical models of cell biology underlying synaptic plasticity. Coding Python.

PhD done @ Bradke lab #NeuroDev #Microtubules

PostDoc in Tchumatchenko group. #SynapticPlasticity #Dendrites
https://github.com/maxschelski/
However, faster MT-RF reduces MT mass noticeably (see graph). Therefore, slowdown of MT-RF in the axon would increase MT mass (which is also what I see in my biophysical model). I would suspect that slowdown of MT-RF could indirectly increase the number of mitochondria in the axon.
November 25, 2024 at 6:21 AM
This could suggest that modifications of the MT array could slow down MT-RF. But even actin could be involved. Actin is at least important to keep the MT array together for homogenous retrograde flow. Depolymerizing actin (LatA) leads to MTs that quickly move both retrogradely and anterogradely.
November 25, 2024 at 6:07 AM
What slows down microtubule retrograde flow (MT-RF) in the axon is an even more open question. It could be the change in MT orientation in the axon - too few microtubules with their plus-ends to the soma. However, I also saw that Taxol slows down MT-RF before changing MT orientation (right side).
November 25, 2024 at 6:07 AM
To make matters even more interesting, I also see that inhibiting Myosin II slows down MT-RF (in the middle). This could indicate that Myosin might also somehow be involved in driving MT-RF.
November 25, 2024 at 5:55 AM
However, I also recruited two different Kinesin motor domains to the plasma membrane. For both motor domains I saw something like faster MT-RF - with a delay after recruiting them to the membrane. I would say, the jury is still out on whether Dynein or Kinesins drive MT-RF physiologically.
November 25, 2024 at 5:55 AM
This would suggest that Dynein could speed up MT-RF through microtubules that have their plus-end towards the soma. One result supporting this, is that recruiting Dynein to the plasma membrane speeds up MT-RF in dendrites (50% plus-ends to soma) but not in axons (2% plus-ends to soma).
November 25, 2024 at 5:55 AM
I also found that recruiting endogous Dynein or an overexpressed Dynein motor domain is sufficient to speed up MT-RF. Recruting a motor deficient point mutant had no effect (see video). I saw the same also for the overexpressed minus-end directed motor domain of KIFC1.
November 25, 2024 at 5:55 AM
I found that acute or chronic inhibition of Dynein slows down MT-RF. This could suggest that Dynein might drive MT-RF in the cell.
November 25, 2024 at 5:55 AM
#Microtubules flow retrogradely in all neurites before axon specification - labeled CAMSAP3 on the right. After axon outgrowth, this retrograde flow slows down - to enable stable axon growth. Could this retrograde flow also exist in #microglia, #astrocytes & #cancer cells? #FluorescenceFriday 🧪 🧠📈
November 22, 2024 at 10:26 AM
Thanks a lot for the post. :) Just as a site note - I also saw the same retrograde movement, when I photoconverted small patches of microtubules (on the right).
November 20, 2024 at 7:59 AM
I also built a simple-to-use #Python toolbox to generate publication-grade movies and figures easily: github.com/maxschelski/.... I optimized it particularly for #microscopy data. Scripts for 25 example figures and 12 movies are available. Documentation under figureflow.readthedocs.io/en/latest/ 🔬🧪📈
November 20, 2024 at 7:46 AM
Hi! I'm Max. I'm developing a #biophysical model of #microtubules in #neurons during #development. The model is based on my surprising experimental finding (lots of live-cell imaging) that the entire microtubule array in neurites flows retrogradely into the soma: www.science.org/doi/10.1126/... 🧪 🧠📈
November 20, 2024 at 7:37 AM