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bioRxiv · 10.1101/2023.07.11.548513

Mark2 phosphorylation of KIF13A at 14-3-3 binding site is required for maintaining TfR vesicle transport dendritically in neuron

Han, Y.·Li, M.·Zhao, B.·Wang, H.·Liu, Y.·Liu, Z.·Xu, J.·Yang, R.
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Abstract

Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a novel kinesin-based mechanism for polarized transport of vesicles to dendrites. SignificanceOur findings suggest that at least one type of vesicles, those containing transferrin receptor, travel exclusively to dendrites and are excluded from axons because the kinase MARK2 phosphorylates the kinesin KIF13A to promote its separation from vesicles at the proximal axon, preventing vesicle transport into axons, such that they travel only to dendrites. Future studies should explore how this mechanism of polarized vesicle transport supports neuronal function.

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Han, Y., Li, M., Zhao, B., Wang, H., Liu, Y., Liu, Z., Xu, J., Yang, R.. 2023-07-12. Mark2 phosphorylation of KIF13A at 14-3-3 binding site is required for maintaining TfR vesicle transport dendritically in neuron. https://doi.org/10.1101/2023.07.11.548513

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