Cytolinker Gas2L1 regulates axon morphology through microtubule-modulated actin stabilization
Dieudonnée van de Willige (Universiteit Utrecht)
Jessica J.A. Hummel (Universiteit Utrecht)
Celine Alkemade (Kavli institute of nanoscience Delft, TU Delft - Applied Sciences, AMOLF Institute for Atomic and Molecular Physics)
Olga I. Kahn (Universiteit Utrecht)
Franco K.C. Au (The Hong Kong University of Science and Technology)
Robert Z. Qi (The Hong Kong University of Science and Technology)
Marileen Dogterom (TU Delft - Applied Sciences, Kavli institute of nanoscience Delft)
Gijsje H. Koenderink (AMOLF Institute for Atomic and Molecular Physics)
Casper C. Hoogenraad (Universiteit Utrecht)
Anna Akhmanova (Universiteit Utrecht)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
Abstract
Crosstalk between the actin and microtubule cytoskeletons underlies cellular morphogenesis. Interactions between actin filaments and microtubules are particularly important for establishing the complex polarized morphology of neurons. Here, we characterized the neuronal function of growth arrest-specific 2-like 1 (Gas2L1), a protein that can directly bind to actin, microtubules and microtubule plus-end-tracking end binding proteins. We found that Gas2L1 promotes axon branching, but restricts axon elongation in cultured rat hippocampal neurons. Using pull-down experiments and in vitro reconstitution assays, in which purified Gas2L1 was combined with actin and dynamic microtubules, we demonstrated that Gas2L1 is autoinhibited. This autoinhibition is relieved by simultaneous binding to actin filaments and microtubules. In neurons, Gas2L1 primarily localizes to the actin cytoskeleton and functions as an actin stabilizer. The microtubule-binding tail region of Gas2L1 directs its actin-stabilizing activity towards the axon. We propose that Gas2L1 acts as an actin regulator, the function of which is spatially modulated by microtubules.
help_outline