Cytolinker Gas2L1 regulates axon morphology through microtubule‐modulated actin stabilization. (5th September 2019)

• Record Type: Journal Article
• Authors: van de Willige, Dieudonnée; Hummel, Jessica JA; Alkemade, Celine; Kahn, Olga I; Au, Franco KC; Qi, Robert Z; Dogterom, Marileen; Koenderink, Gijsje H; Hoogenraad, Casper C; Akhmanova, Anna
• Is Part Of: EMBO reports. Volume 20:Number 11(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-05
• Subjects: axon -- cytolinker -- cytoskeleton -- in vitro reconstitution -- neuronal development; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201947732
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: The actin‐microtubule crosslinking protein Gas2L1 stimulates axon branching and reduces axon outgrowth through microtubule‐modulated actin stabilization. Cytolinker Gas2L1 stabilizes actin, stimulates axon branching and reduces axon outgrowth in rat primary hippocampal neurons. Gas2L1 is autoinhibited by an interaction between its actin‐ and microtubule‐binding domains. In vitro, autoinhibition of Gas2L1 is relieved by reciprocal binding to actin filaments and microtubules. The microtubule‐binding tail region of Gas2L1 targets its actin‐stabilizing activity towards the axon. Abstract : The actin‐microtubule crosslinking protein Gas2L1 stimulates axon branching and reduces axon outgrowth through microtubule‐modulated actin stabilization.