| First Author | Alsabban AH | Year | 2020 |
| Journal | EMBO J | Volume | 39 |
| Issue | 1 | Pages | e101090 |
| PubMed ID | 31746486 | Mgi Jnum | J:286227 |
| Mgi Id | MGI:6387447 | Doi | 10.15252/embj.2018101090 |
| Citation | Alsabban AH, et al. (2020) Kinesin Kif3b mutation reduces NMDAR subunit NR2A trafficking and causes schizophrenia-like phenotypes in mice. EMBO J 39(1):e101090 |
| abstractText | The transport of N-methyl-d-aspartate receptors (NMDARs) is crucial for neuronal plasticity and synapse formation. Here, we show that KIF3B, a member of the kinesin superfamily proteins (KIFs), supports the transport of vesicles simultaneously containing NMDAR subunit 2A (NR2A) and the adenomatous polyposis coli (APC) complex. Kif3b(+/-) neurons exhibited a reduction in dendritic levels of both NR2A and NR2B due to the impaired transport of NR2A and increased degradation of NR2B. In Kif3b(+/-) hippocampal slices, electrophysiological NMDAR response was found decreased and synaptic plasticity was disrupted, which corresponded to a common feature of schizophrenia (SCZ). The histological features of Kif3b(+/-) mouse brain also mimicked SCZ features, and Kif3b(+/-) mice exhibited behavioral defects in prepulse inhibition (PPI), social interest, and cognitive flexibility. Indeed, a mutation of KIF3B was specifically identified in human SCZ patients, which was revealed to be functionally defective in a rescue experiment. Therefore, we propose that KIF3B transports NR2A/APC complex and that its dysfunction is responsible for SCZ pathogenesis. |
