Genetic ablation of dynactin p150Glued in postnatal neurons causes preferential degeneration of spinal motor neurons in aged mice

Molecular Neurodegeneration
Jia YuHuaibin Cai

Abstract

Dynactin p150Glued, the largest subunit of the dynactin macromolecular complex, binds to both microtubules and tubulin dimers through the N-terminal cytoskeleton-associated protein and glycine-rich (CAP-Gly) and basic domains, and serves as an anti-catastrophe factor in stabilizing microtubules in neurons. P150Glued also initiates dynein-mediated axonal retrograde transport. Multiple missense mutations at the CAP-Gly domain of p150Glued are associated with motor neuron diseases and other neurodegenerative disorders, further supporting the importance of microtubule domains (MTBDs) in p150Glued functions. However, most functional studies were performed in vitro. Whether p150Glued is required for neuronal function and survival in vivo is unknown. Using Cre-loxP genetic manipulation, we first generated a line of p150Glued knock-in mice by inserting two LoxP sites flanking the MTBD-coding exons 2 to 4 of p150Glued-encoding Dctn1 gene (Dctn1LoxP/), and then crossbred the resulting Dctn1LoxP/ mice with Thy1-Cre mice to generate the bigenic p150Glued (Dctn1LoxP/LoxP; Thy1-Cre) conditional knockout (cKO) mice for the downstream motor behavioral and neuropathological studies. P150Glued expression was completely abolished in Cre-expressin...Continue Reading

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Citations

Feb 6, 2020·Annals of Clinical and Translational Neurology·Wo-Tu TianLi Cao
Dec 19, 2019·Brain : a Journal of Neurology·Virenkumar A Pandya, Rickie Patani
Jun 10, 2020·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Sep 24, 2020·Journal of Neurochemistry·Melina OverhoffNatalia L Kononenko
Dec 8, 2020·Frontiers in Cellular Neuroscience·María José Castellanos-MontielThomas M Durcan
Feb 14, 2021·Cells·Sara Marmolejo-Martínez-ArteseroDavid Romeo-Guitart
Apr 27, 2021·Technology in Cancer Research & Treatment·Xiaotao SuChao Qin
Oct 8, 2021·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Ji HeDongsheng Fan

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Methods Mentioned

BETA
biopsy
PCR
density gradient centrifugation
acetylation

Software Mentioned

NIH ImageJ
Field
GraphPad
Freehand
GraphPad Prism
Flex
Polygon
ImageJ

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