{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T17:14:13Z","timestamp":1793553253427,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011839","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070725"],"award-info":[{"award-number":["32070725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31171007"],"award-info":[{"award-number":["31171007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471038"],"award-info":[{"award-number":["32471038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>The harmony of neuronal excitation and inhibition is essential for precise neuronal circuitry in the developmental brain, and thus affects the human emotion. Abnormalities of synaptic morphology directly affect neuronal function and contribute to a variety of psychiatric disorders. Previous studies have shown that <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> (Kinesin-12), a microtubule-associated motor protein, affects neurite growth, navigation, and branching during neuronal development, revealing the potential of <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> to influence neuronal dendritic morphology. A GWAS study in a European population showed that there were variants in both exons and introns of the <jats:italic>KIF15<\/jats:italic> gene on chromosome 3 in patients with depression. Therefore, we generated <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice using CRISPR\/Cas9 technology. In this study, we found that <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice have exhibited significant impacts on dendritic morphology and function, which contributes to mood disorders. Compared with <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> wild-type mice, adolescent <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice showed a significant decrease in the excitatory postsynaptic scaffolding protein PSD95 and NMDA receptors, as well as a reduction in the total density of dendritic spines and the density of mushroom spines, and a decrease in the frequency of mEPSCs. Meanwhile, the inhibitory postsynaptic scaffold protein Gephyrin and GABRB1 significantly upregulated. However, the adult <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice simultaneously exhibited an obvious manic behavior and their PSD95 expression increased rapidly, even more than that of the <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> wild-type mice. Meanwhile, overexpression of <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> in <jats:italic><jats:italic>kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> zebrafish rescued their depressive behavior. In terms of molecular mechanism, we showed that KIF15 interacted with PSD95 protein using both endogenous and exogenous Co-IP assays. Furthermore, we found that PSD95 in <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice was distributed around neuronal nuclei, in contrast to PSD95 localized close to the cell membrane in <jats:italic><jats:italic>Kif15<\/jats:italic><\/jats:italic> wild-type mice. In conclusion, our study has identified a microtubule-associated molecular motor, KIF15, that plays a novel role in bipolar disorder through its contributions to spine morphology and function.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011839","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:55:26Z","timestamp":1756835726000},"page":"e1011839","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deficiency of Kif15 impairing synaptic development leads to mood disorder in 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