Scientists determine a brand new change for controlling motor proteins

Inside neurons, motor proteins haul valuable cargo, transferring important items alongside thread-like roadways referred to as microtubule tracks.

This miniature freeway system is important for holding neurons wholesome: When site visitors is flowing nicely, important supplies are in a position to attain distant areas of the cells the place they’re wanted. When the system breaks down, it will possibly impede mobile operate and result in cell dying.

Now, scientists have recognized a brand new instrument for site visitors management. In a research revealed in December 2021 within the journal Growth, researchers describe how an enzyme referred to as GSK3β can act as a cease change for a sort of motor protein referred to as kinesin 1.

Our publication particulars how GSK3β attaches a molecular tag to kinesin 1 motors, which causes the motors to cease with out detaching from microtubule tracks. We’re tremendous excited, since now we all know the way to management the ‘engine’ whereas it’s transferring on a observe.”


Shermali Gunawardena, Senior Creator, PhD, Affiliate Professor, Organic Sciences, College at Buffalo School of Arts and Sciences

“Transport of cargoes by motors is a tightly coordinated course of, and but the molecular mechanisms that management these ‘engines’ alongside the microtubule tracks stay largely unknown,” says the research’s first writer, Rupkatha Banerjee, PhD, a postdoctoral analysis affiliate at Scripps Analysis in Florida who accomplished her doctorate in organic sciences at UB.

“Our work gives an in-depth understanding of how the enzyme GSK3β acts as a key regulator of the kinesin 1 motor,” Banerjee provides. “Particularly, we’ve recognized a exact web site on kinesin 1 that’s modified by GSK3β. Utilizing molecular biology, in vitro evaluation and fly genetics, coupled with in vivo imaging strategies, we have been in a position to tease out the mechanistic particulars by which disruption of this specific web site impacts motor motion and motor attachment to cargoes or microtubule tracks in an entire organism.”

The findings -; based mostly on laboratory experiments, together with some within the neurons of fruit fly larvae -; might open the door for future analysis on pausing motors as a mechanism for treating ailments.

Gunawardena highlights most cancers as one potential instance: “In most cancers, cells are quickly dividing, and motors are concerned on this. So if you happen to can cease the motors, you may influence this steady division of cells,” she says.

From a special angle, she notes that, “in some neurodegenerative ailments, you see blockages of cargo inside neurons as a result of issues are getting caught on the street. If we are able to management the motors and cease them, perhaps we may also help to clear the observe and eliminate these blockages. In elements of California, at rush hour, you might have site visitors lights that solely let so many vehicles in at a sure time to stop the freeway from getting too full, which might decelerate site visitors and trigger site visitors blocks. Maybe we are able to additionally apply this idea in neurons, too, if we are able to management motors by turning them on or off.”

Co-authors of the research additionally embody Piyali Chakraborty, a MS graduate of UB’s neuroscience program, and Michael C. Yu, PhD, affiliate professor of organic sciences at UB.

Along with detailing how GSK3β can cease kinesin 1 motors, the analysis explored different facets of the enzyme’s interplay with the motors, with outcomes underscoring the concept that GSK3β performs an necessary function in fine-tuning kinesin 1 motor motion inside neurons inside a residing organism.

“This publication emphasizes fine-tuning of motor operate as a possible strategy for restoring transport defects that contribute to neurodegeneration and most cancers,” Banerjee says.

The analysis was supported by the Nationwide Institute of Neurological Issues and Stroke, a part of the Nationwide Institutes of Well being; the John R. Oishei Basis; and the Mark Diamond Analysis Fund at UB.

Supply:

Journal reference:

Banerjee, R., et al. (2021) A cease or go change: glycogen synthase kinase 3β phosphorylation of the kinesin 1 motor area at Ser314 halts motility with out detaching from microtubules. Growth. doi.org/10.1242/dev.199866

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