Motor neuron diseases are a group of progressive neurological disorders that destroy motor neurons, the cells that control voluntary muscles for such activities as speaking, walking, breathing, and swallowing. When these neurons die, the muscle itself atrophies. A well-known motor neuron disease is amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig's disease).
Possible models for the bi-directional movement observed in the dynein-dynactin molecular motor along microtubules. A) Random, diffusive motions; B) Flexible rotation of the dynein ring; and C) Steps dictated by the microtubule lattice. Credit: Jennifer L. Ross, PhD, University of Pennsylvania School of Medicine; Nature Cell Biology
Using a specially-constructed microscope that allows researchers to observe the action of one macromolecule at a time, the team found that a protein motor is able to move back and forth along a microtubule – a molecular track – rather than in one direction, as previously thought. They report their findings in a recent issue of Nature Cell Biology. The proteins in this motor, dynein and dynactin, are the "long-distance truckers" of the cell: working together, they are responsible for transporting cellular cargo from the periphery of a cell toward its nucleus.
"My lab concentrates on the cellular and genetic aspects of the dynein-dynactin motor, while Yale's group delves into the mechanics of the motor itself," says Holzbaur. "We're deconstructing the system to understand how it all works in a living cell. In the lab, we start with a clean microtubule with a motor walking across it, but in the cell it's different: microtubules are packed together, with proteins studded along them, and cellular organelles and mitochondria are crammed in. The motor needs to maneuver around those 'obstructions.'" Goldman and Holzbaur suggest that the ability of the dynein-dynactin motor to move in both directions along the microtubule may provide the necessary maneuvering ability to allow for effective long distance transport.
Earlier this year, as reported in The Journal of Cell Biology, researchers in Holzbaur's lab found that a mutation in dynactin leads to degeneration of motor neurons, the hallmark of motor neuron disease. This mutation decreases the efficiency of the dynein-dynactin motor in "taking out the trash" of the cell, and thus leads to the accumulation of misfolded proteins in the cell, which may in turn lead to the degeneration of the neuron.
Scientists are now finding that many other molecular motors are remarkably flexible in their behavior. In several further papers published in the Proceedings of the National Academy of Sciences and The EMBO Journal, Goldman and colleagues at the University of Illinois found that a "local delivery" motor, termed myosin V, moves cargo with a variable path short distances along another type of cellular track called actin. This flexibility could help myosin V navigate crowded regions of the cell where the actin filaments criss-cross and where other cellular components would otherwise pose an impediment to motion. Defects in myosin V function also result in neurological defects.
Most of these molecular motors are associated with specific diseases or developmental defects, so understanding the puzzling aspects of their behavior in detail is necessary for building nanotechnological machines that, for example, could replace defective motors. "The ultimate goal is to find ways to treat motor neuron disease as well as other diseases that involve cellular motors and also construct nano-scale machines based on these biological motors," says Goldman.
Karen Kreeger | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy