Protrudin functions as a scaffold in the endoplasmic reticulum to support axon regeneration in the adult central nervous system
Protrudin functions as a scaffold in the endoplasmic reticulum to support axon regeneration in the adult central nervous system
Summary Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.
Petrova Veselina、Pearson Craig S.、Eva Richard、Fawcett James W.、Williams Pete A.、Reid Evan、Tribble James R.、Geller Herbert M.、Solano Andrea G.
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of CambridgeLaboratory of Developmental Neurobiology, Division of Intramural Research Lung and Blood InstituteJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of CambridgeJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge||Centre for Reconstructive Neuroscience, Institute of Experimental Medicine CASDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetCambridge Institute for Medical Research and Department of Medical Genetics, University of CambridgeDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska InstitutetLaboratory of Developmental Neurobiology, Division of Intramural Research Lung and Blood InstituteLaboratory of Developmental Neurobiology, Division of Intramural Research Lung and Blood Institute
基础医学神经病学、精神病学细胞生物学
Axon regenerationProtrudinendoplasmic reticulumaxon transportoptic nerveneuroprotection
Petrova Veselina,Pearson Craig S.,Eva Richard,Fawcett James W.,Williams Pete A.,Reid Evan,Tribble James R.,Geller Herbert M.,Solano Andrea G..Protrudin functions as a scaffold in the endoplasmic reticulum to support axon regeneration in the adult central nervous system[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2020.01.15.907550.点此复制
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