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The movements of neurons have been shown to be caused by the pushing and pulling of motor proteins


Using fluorescent single-molecule microscopy, pictured here, researchers observe how motor proteins move along the microtubule. Researchers observe individual fluorescently-tagged proteins and DNA molecules using high-power cameras and lenses. Credit: Jeff Shaw/Penn State

Neurons, which are responsible for producing the signals that ultimately lead to an action such as speaking or moving a muscle, are built and maintained by classes of motor proteins that transport molecular cargo along long pathways called microtubules. A Penn State-led team of researchers has revealed how two major groups of motor proteins compete to transport cargo in opposite directions between the cell body and synapses in neurons.

Through single-molecule fluorescence microscopy and computational modeling, the group investigated how three classes of one type of motor protein, known as kinesins, interact with another type of motor, a dynein, during cargo transportation. Their findings have been published in eLifecould help scientists better understand the normal cargo transport process and, in future work, show how it gets disrupted in the case of neurodegenerative diseases, such as Alzheimer’s disease.

“Kinesin and dynein move along microtubules, which are more than 1,000 times smaller than a hair piece,” said corresponding author William Hancock, MD, professor of biomedical engineering (BME) at Penn State. “Because of the structural polarity of the microtubules, kinesin motors bind to a charge and pull it in one direction, carrying it towards the synapse, while dynein binds and moves in the opposite direction, to the cell body of neurons. When both motors bind to a cargo at the same time, competition between them ensues. the two engines, and how each performs determines how fast and in what direction the charge will travel.”

There are about ten different types of transports divided into three families, while there is only one type of transports dynein. The researchers took one kinesin motor from each of the three families and attached it to dynein. Using single-molecule fluorescence microscopy — in which scientists observe individual fluorescently labeled proteins and DNA molecules using high-powered cameras and lenses — they observed how the proteins moved along the microtubule.

“Each of the Kennesen’s engines is like a different kind of car on the road: one is a race car, one is an SUV, one is a truck,” Hancock said. “Some kinesin motors move short distances, some move long distances, some move faster and some move slower. Because the motors perform so differently from one another, we were surprised by what we found when we linked them together with dynein.”

Despite the apparent differences, the researchers found that all three types of kinesin performed equivalently against dynein: they all effectively countered crippling dynein loads.

To better understand the underlying mechanism, the researchers took their experimental results and developed a computational model, which indicated that the three types of kinesin use different ways to compete against dynein.

Kinesin-1 motors pull firmly against dynein, rarely disengaging from the microtubule pathway, but taking some time to set up again. Kinesin-3 motors disengage easily when pulled against dynein, but attach back to the microtubule track quickly, taking less than a split second to start moving again. Kinesin-2 drives show a mixture of kinesin-1 and -3 behaviours.

Experimental results indicate that it is not the mechanical properties of kinesin that determine the direction and velocity of cargo transport; Another thing is playing.

“The discovery that kinesin-3 drives back on track within milliseconds is startling, and we want to confirm and understand the biophysical mechanisms behind this rapid association,” Hancock said. “We also plan to look at the regulation of the adapter molecules that attach protein motors to their cargo, as well as the mechanical stiffness of the cargo, to see if these factors play a role.”

To do this, the researchers will put the motors under different mechanical loads by attaching them to proteins with longer and longer pieces of DNA, while analyzing their motions under a microscope.

Understanding the intracellular transport system, as well as its susceptibility to mutations, could help scientists make progress in the study of neurodegenerative conditions such as Alzheimer’s disease, Huntington’s disease, and Lou Gehrig’s disease.

“It is clear that defects in intracellular transport are important aspects of neurodegenerative diseases, but the underlying mechanisms and how transport defects contribute to pathology are unclear,” Hancock said. “With these new insights into the kinesin’s kinetic mechanisms, we hope to explain how mutations affect its ability to transmit and thus harm the health of neurons.”

more information:
Allison M Gicking et al, Kinesin-1, -2 and -3 use family-specific chemomechanical strategies to compete effectively with Dynein during bidirectional transport, eLife (2022). DOI: 10.7554/eLife.82228

Journal information:

Provided by Penn State University

the quote: Movements of neurons shown to result from the pushing and pulling of motor proteins (2023, April 12) Retrieved April 12, 2023 from https://phys.org/news/2023-04-neuron-movements-shown-motor-proteins. html

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