Tau Islands, Actin Locks, and Automated Kymograph Analysis

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Cohesive Tau Islands Shield and Protect the Microtubule Lattice

Tau, a microtubule-associated protein in the brain, is primarily recognized for its role in neurodegenerative diseases. In fact, the term “tauopathy” was specifically coined to reference neuronal disorders pathologically defined by tau protein aggregates. But what is the physiological function of tau in healthy neurons? This question has largely alluded researchers to date and is made more intriguing in that tau is an intrinsically disordered protein with microtubule-regulating capabilities.

The Ori-McKenney/McKenney and Lánský/Braun research groups explore the mechanism and function of tau-mediated microtubule regulation in a pair of papers published in Nature Cell Biology. Using in vitro reconstitution approaches, the authors find that tau self-organizes into cohesive “islands” that shield and protect the microtubule lattice. Tau islands prevent severing enzymes (i.e. katanin and spastin) from accessing microtubule surfaces and function as roadblocks against molecular motors (i.e. kinesin-1). More processive motors (i.e. kinesin-8 and dynein), however, can penetrate the islands, revealing that self-associated tau molecules form a selectively permissible barrier. Collectively, these studies provide a framework for understanding tau functions in physiological and disease-states.

“We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behavior and potentially compete with tau in regulating access to the microtubule surface.”
–Siahaan et al.

Tools and Methods

KymoButler, A Deep Learning Software For Automated Kymograph Analysis

Jakobs, Dimitracopoulos, and Franze  |  eLife
A new software package harnesses Machine Learning for the automated analysis of dynamic biological processes.

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• Actin-microtubule crosslinks determine the viscoelasticity of cytoskeleton composites.
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