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. |