Efa6 regulates axon growth, branching and maintenance by eliminating off-track microtubules at the cortex
Efa6 regulates axon growth, branching and maintenance by eliminating off-track microtubules at the cortex
Abstract Axons are the enormously long, cable-like neuronal extensions that wire our nervous system. The formation and plastic maintenance of these delicate structures requires parallel bundles of microtubules (MTs), which form the structural backbones and highways for life-sustaining transport in axons. In ageing and certain axonopathies, axonal MTs lose their bundled appearances forming areas of disorganisation. We use Drosophila to study various mechanisms that promote axonal MT bundle organisation and dynamics during development and maintenance. Here we report important roles of the membrane-associated protein Efa6 in axonal MT regulation relevant for axonal growth, branching and MT bundle maintenance. Efa6 acts as a typical cortical MT collapse factor by eliminating MTs that approach the axonal plasma membrane. This action abolishes MTs that have left the axon bundle, thus providing a quality control mechanism that prevents MT disorganisation during the formation and maintenance of axons. Furthermore, we find this action to reduce axonal growth and branch formation in cultured neurons and in vivo. Using structure-function analyses, we show that cytoplasmic localisation of a small N-terminal peptide motif alone is sufficient to eliminate entire MT networks in mouse fibroblasts, and loss of whole axons in Drosophila primary neurons. This highly destructive activity becomes meaningful when restricted to the cell plasma membrane via the plekstrin homology domain present in the Efa6 C-terminus. Our data provide a paradigm for the fundamental and disease-relevant role of cortical collapse factors in neurons.
Qu Yue、Parkin Jill、Dorey Karel、Voelzmann Andr¨|、Allan Viki、Prokop Andreas、Ramos Pilar Okenve、Rathbone Alex、Lees Meredith、Friel Claire、Hahn Ines、Sanchez-Soriano Natalia
The University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of LiverpoolThe University of Nottingham, School of Life Sciences, Faculty of Medicine & Health SciencesThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyThe University of Nottingham, School of Life Sciences, Faculty of Medicine & Health SciencesThe University of Manchester, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, School of BiologyDepartment of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool
细胞生物学分子生物学
Drosophilaneurodegenerationaxonsactincytoskeletonmicrotubules
Qu Yue,Parkin Jill,Dorey Karel,Voelzmann Andr¨|,Allan Viki,Prokop Andreas,Ramos Pilar Okenve,Rathbone Alex,Lees Meredith,Friel Claire,Hahn Ines,Sanchez-Soriano Natalia.Efa6 regulates axon growth, branching and maintenance by eliminating off-track microtubules at the cortex[EB/OL].(2025-03-28)[2025-06-19].https://www.biorxiv.org/content/10.1101/385658.点此复制
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