Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination
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Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination. / Konietzny, Anja; Han, Yuhao; Popp, Yannes; van Bommel, Bas; Sharma, Aditi; Delagrange, Philippe; Arbez, Nicolas; Moutin, Marie-Jo; Peris, Leticia; Mikhaylova, Marina.
in: J CELL SCI, Jahrgang 137, Nr. 8, jcs261737, 15.04.2024.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination
AU - Konietzny, Anja
AU - Han, Yuhao
AU - Popp, Yannes
AU - van Bommel, Bas
AU - Sharma, Aditi
AU - Delagrange, Philippe
AU - Arbez, Nicolas
AU - Moutin, Marie-Jo
AU - Peris, Leticia
AU - Mikhaylova, Marina
N1 - © 2024. Published by The Company of Biologists Ltd.
PY - 2024/4/15
Y1 - 2024/4/15
N2 - 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.
AB - 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.
KW - Animals
KW - Microtubules/metabolism
KW - Axonal Transport
KW - Tyrosine/metabolism
KW - Lysosomes/metabolism
KW - Mice
KW - Mice, Knockout
KW - Axons/metabolism
KW - Endosomes/metabolism
KW - Neurons/metabolism
U2 - 10.1242/jcs.261737
DO - 10.1242/jcs.261737
M3 - SCORING: Journal article
C2 - 38525600
VL - 137
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 8
M1 - jcs261737
ER -