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Publication : Axonal transport of Frizzled5 by Alcadein α-containing vesicles is associated with kinesin-1.

First Author  Shiraki Y Year  2023
Journal  Mol Biol Cell Volume  34
Issue  11 Pages  ar110
PubMed ID  37585286 Mgi Jnum  J:342467
Mgi Id  MGI:7545387 Doi  10.1091/mbc.E22-10-0495
Citation  Shiraki Y, et al. (2023) Axonal transport of Frizzled5 by Alcadein alpha-containing vesicles is associated with kinesin-1. Mol Biol Cell 34(11):ar110
abstractText  Alcadein alpha (Alcalpha) and amyloid-beta protein precursor (APP) are cargo receptors that associate vesicles with kinesin-1. These vesicles, which contain either Alcalpha or APP, transport various proteins/cargo molecules into axon nerve terminals. Here, we analyzed immune-isolated Alcalpha- and APP-containing vesicles of adult mouse brains with LC-MS/MS and identified proteins present in vesicles that contained either Alcalpha or APP. Among these proteins, Frizzled-5 (Fzd5), a Wnt receptor, was detected mainly in Alcalpha vesicles. Although colocalization ratios of Fzd5 with Alcalpha are low in the neurites of differentiating neurons by a low expression of Fzd5 in embryonic brains, the suppression of Alcalpha expression decreased the localization of Fzd5 in neurites of primary cultured neurons. Furthermore, Fzd5-EGFP expressed in primary cultured neurons was preferentially transported in axons with the transport velocities of Alcalpha vesicles. In synaptosomal fractions of adult-mice brains that express higher levels of Fzd5, the amount of Fzd5 and the phosphorylation level of calcium/calmodulin-dependent protein kinase-II were reduced in the Alcalpha-deficient mice. These results suggest that reduced transport of Fzd5 by Alcalpha-containing vesicles associated with kinesin-1 in axon terminals may impair the response to Wnt ligands in the noncanonical Ca(2+)-dependent signal transduction pathway at nerve terminals of mature neurons.
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