Journal Article PUBDB-2024-05659

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Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination

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2024
Company of Biologists Limited Cambridge

Journal of cell science 137(8), jcs261737 () [10.1242/jcs.261737]
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Abstract: In neurons, the microtubule (MT) cytoskeleton forms the basis for long-distance protein transport from the cell body into and out of dendrites and axons. To maintain neuronal polarity, the axon initial segment (AIS) serves as a physical barrier, separating the axon from the somatodendritic compartment and acting as a filter for axonal cargo. Selective trafficking is further instructed by axonal enrichment of MT post-translational modifications, which affect MT dynamics and the activity of motor proteins. Here, we compared two knockout mouse lines lacking the respective enzymes for MT tyrosination and detyrosination, and found that both knockouts led to a shortening of the AIS. Neurons from both lines also showed an increased immobile fraction of endolysosomes present in the axon, whereas mobile organelles displayed shortened run distances in the retrograde direction. Overall, our results highlight the importance of maintaining the balance of tyrosinated and detyrosinated MTs for proper AIS length and axonal transport processes.

Classification:

Contributing Institute(s):
  1. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) - Kay Grünewald (CSSB-LIV-KG)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)
  2. DFG project G:(GEPRIS)390688087 - EXC 2049: Comprehensive approaches to neurological and psychiatric disorders "NeuroCure" (390688087) (390688087)
Experiment(s):
  1. No specific instrument

Appears in the scientific report 2024
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 Record created 2024-08-30, last modified 2025-07-23


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