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• W2984072224 abstract "Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through the ARF activator Efa6 in C. elegans, and by neurodevelopmental disorders linked to the mammalian kinesin Kif21A. How cortical collapse factors influence axon growth is little understood. Here we studied them, focussing on the function of Drosophila Efa6 in experimentally and genetically amenable fly neurons. First, we show that Drosophila Efa6 can inhibit MTs directly without interacting molecules via an N-terminal 18 amino acid motif (MT elimination domain/MTED) that binds tubulin and inhibits microtubule growth in vitro and cells. If N-terminal MTED-containing fragments are in the cytoplasm they abolish entire microtubule networks of mouse fibroblasts and whole axons of fly neurons. Full-length Efa6 is membrane-attached, hence primarily blocks MTs in the periphery of fibroblasts, and explorative MTs that have left axonal bundles in neurons. Accordingly, loss of Efa6 causes an increase of explorative MTs: in growth cones they enhance axon growth, in axon shafts they cause excessive branching, as well as atrophy through perturbations of MT bundles. Efa6 over-expression causes the opposite phenotypes. Taken together, our work conceptually links molecular and sub-cellular functions of cortical collapse factors to axon growth regulation and reveals new roles in axon branching and in the prevention of axonal atrophy. Furthermore, the MTED delivers a promising tool that can be used to inhibit MTs in a compartmentalised fashion when fusing it to specifically localising protein domains." @default.
• W2984072224 created "2019-11-22" @default.
• W2984072224 creator A5031538002 @default.
• W2984072224 creator A5036049078 @default.
• W2984072224 creator A5039416756 @default.
• W2984072224 creator A5041209830 @default.
• W2984072224 creator A5069766453 @default.
• W2984072224 creator A5070660949 @default.
• W2984072224 creator A5074423476 @default.
• W2984072224 creator A5074904088 @default.
• W2984072224 creator A5076925163 @default.
• W2984072224 creator A5084821328 @default.
• W2984072224 creator A5085393594 @default.
• W2984072224 creator A5086144872 @default.
• W2984072224 date "2019-11-13" @default.
• W2984072224 modified "2023-10-02" @default.
• W2984072224 title "Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex" @default.
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