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Cellular Motility: Microtubules, Motor Proteins and Tau-Proteins

Cellular motility is based on motor-proteins that can bind to filamentous scaffold proteins and – under consumption of ATP – can “crawl” on these filaments. This note is about proteins connected to microtubules, one of the filamentous structures that compose the cytoskeleton. Microtubules are hollow tubes of ca 25nm, composed of tubulin-heterodimers. The proteins are polymerized in a directed fashion, allowing to differentiate a plus-end and a minus-end of the fiber. Another important scaffold component that is also involved in movements, are actin fibers that cooperate with myosin as a motor-protein. The best known movement involving the actin-myosin system is muscular contraction.

There are two classes of motor molecules that travel on tubulin: kinesins (mostly anterograde movement) and dyneins (retrograde movements). Microtubules are stabilized by interaction of Tauproteins, that are also known as origin of a series of severe neurodegenerative diseases, including Alzheimer’s disease.

Image: Rat cortical neurons (prim. culture). Max. projection. Nuclei (Dapi, blue), Nestin (Cy2, green), DCX (Cy3, red), ßIII-tubulin (Cy5, white). Imaged with a TCS SP8.

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Freight Traffic in Nerve Cells

One main role of intracellular motility is the need to transport materials between organelles or different parts of the cell. For a review see [1]. A special type of transport in neurons is the axonal transport of cargo, based on the microtubule network. There are two different speeds of transport: a slow type, which is responsible for transport of proteins and enzymes and a fast transport that moves vesicles mainly containing neurotransmitters. These vesicles are produced in the cell soma and subsequently transported through the axon to the point where they are needed: the synapses, which occurs via anterograde transport by kinesin moving on tubulin. Other molecules, such as metabolic products, membrane material, and nerve growth factors are transported in the opposite, retrograde direction, via dynein moving on tubulin [2].

Neurodegeneration and Cancer: contributions by deficient Axonal Transport?

The McKenney Lab at the University of California, Davis is interested in how cells internally organize using molecular motor proteins, with a focus on the microtubule cytoskeleton and the motor proteins that use this filament system for transport (kinesins and dyneins). Topics of interest include allosteric regulation of motor protein movement, how motor activity is balanced and coordinated, and how dysfunction in motor activity leads to human diseases such as cancer and neurodegeneration.

The Leica TCS SPE II is a high-resolution spectral confocal microscope, which has allowed the McKenney lab to uncover novel insights into the localization and function of proteins that regulate molecular motor transport, crucial for neuronal function [3].

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