Researchers at the University of Pennsylvania School of Medicine discovered that proteins carrying chemical cargo in nerve cells react differently when exposed to the tau protein, which plays an important role in Alzheimer’s disease.
Dynein and kinesin proteins transport cellular cargo towards opposite ends of tracks called microtubules. Tau binds to the microtubule surface and acts like a speed bump to regulate protein traffic, the group found. “But it is a smart speed bump because it impedes these different motor proteins to different degrees,” explains first author Ram Dixit, PhD, a postdoctoral fellow in the lab of senior author Erika Holzbaur, PhD, Professor of Physiology.
“Our findings show a mechanism of regulating the transport of nutrients, signaling molecules, and waste proteins along a nerve cell’s axon,” says Dixit. “Neurodegenerative diseases such as Alzheimer’s arise when pieces of this shipping system goes awry.”
The transport performed by dynein and kinesin is required for continuously providing new proteins to the axon and synapse to maintain normal cellular function, and is also required to remove old, misfolded, or aggregated proteins for degradation. Just as important, this transport is required for moving other proteins from the nerve-cell synapse back to the cell body, which is also required to maintain healthy neurons.
In neurons, microtubules are abundantly decorated with tau. Dynein and kinesin encounter the tau molecules on their travels along the microtubules. The Penn group found that dynein, which carries loads towards the interior of the cell, maneuvers around tau; whereas, kinesin, which carries loads towards the outside of the cell, detaches when it encounters tau.
These findings appear online January 17 in Science in advance of print publication.
Dynein and kinesin’s individual maneuverings when encountering tau allow for the cell to be able to offload cargo where it needs to go with fine-tune accuracy. “Tau may determine where kinesin offloads cargo along the microtubule tracks that radiate out to the cell surface from the center,” says Holzbaur. “And dynein’s ability to back up and go around when it encounters an obstacle such as tau may be a mechanism to ensure that it gets to the center of the cell with its important cargo.”
The group conducted studies using single molecules moving along a tau-decorated microtubule to determine the effects of tau on dynein and kinesin’s movement. Mutations in molecular motors such as dynein and kinesin can lead to degeneration of neurons. These mutations, for example, decrease the efficiency of dynein and kinesin. This problem can lead to the accumulation of misfolded proteins in the cell, which, in turn may lead to the degeneration of the neuron.
“There’s a growing theme that defects in transport are tightly associated with neurodegeneration,” says Holzbaur. “It’s already been shown in Alzheimer’s disease that there is a change in the distribution of tau along microtubules. Instead of kinesin getting its cargo closer to the cell’s outer surface, tau accumulates in the cell body and kinesin’s cargo of newly synthesized proteins gets dropped early, not at the cell surface, thus causing problems. Our findings explain how that can happen.”
Karen Kreeger | EurekAlert!
Deep stimulation improves cognitive control by augmenting brain rhythms
04.04.2019 | Picower Institute at MIT
Black nanoparticles slow the growth of tumors
04.04.2019 | Technische Universität München
A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter
A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.
Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...
The technology could revolutionize how information travels through data centers and artificial intelligence networks
Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...
Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.
Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...
Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna
A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...
17.04.2019 | Event News
15.04.2019 | Event News
09.04.2019 | Event News
18.04.2019 | Life Sciences
18.04.2019 | Physics and Astronomy
18.04.2019 | Life Sciences