TY - JOUR
T1 - Cytolinker Gas2L1 regulates axon morphology through microtubule-modulated actin stabilization
AU - van de Willige, Dieudonnée
AU - Hummel, Jessica J.A.
AU - Alkemade, Celine
AU - Kahn, Olga I.
AU - Au, Franco K.C.
AU - Qi, Robert Z.
AU - Dogterom, Marileen
AU - Koenderink, Gijsje H.
AU - Hoogenraad, Casper C.
AU - Akhmanova, Anna
PY - 2019/11/5
Y1 - 2019/11/5
N2 - 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.
AB - 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.
KW - axon
KW - cytolinker
KW - cytoskeleton
KW - in vitro reconstitution
KW - neuronal development
UR - http://www.scopus.com/inward/record.url?scp=85071752811&partnerID=8YFLogxK
U2 - 10.15252/embr.201947732
DO - 10.15252/embr.201947732
M3 - Article
C2 - 31486213
AN - SCOPUS:85071752811
SN - 1469-221X
VL - 20
JO - EMBO Reports
JF - EMBO Reports
IS - 11
M1 - e47732
ER -