KIF5B plays important roles in dendritic spine plasticity and dendritic localization of PSD95 and FMRP in the mouse cortex in vivo

Kinesin 1 (KIF5) is one major type of motor protein in neurons, but its members’ function in the intact brain remains less studied. Using in vivo two-photon imaging, we find that conditional knockout of Kif5b (KIF5B cKO) in CaMKIIα-Cre-expressing neurons shows heightened turnover and lower stability...

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Published in:	Cell reports (Cambridge) Vol. 43; no. 3; p. 113906
Main Authors:	Fok, Albert Hiu Ka, Huang, Yuhua, So, Beth Wing Lam, Zheng, Qiyu, Tse, Chun Sing Carlos, Li, Xiaoyang, Wong, Kenneth Kin-Yip, Huang, Jiandong, Lai, Kwok-On, Lai, Cora Sau Wan
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 26-03-2024 Elsevier
Subjects:	Animals CP: Neuroscience dendritic spine Dendritic Spines - metabolism Extinction, Psychological Fear fear learning FMRP Fragile X Mental Retardation Protein - genetics Fragile X Mental Retardation Protein - metabolism Fragile X Syndrome - metabolism frontal association cortex gephyrin in vivo two-photon imaging KIF5B kinesin-1 Mice Mice, Inbred C57BL Mice, Knockout Neuronal Plasticity PSD95 synaptic protein translocation frontal association cortex in vivo two-photon imaging PSD95 kinesin-1 FMRP CP: Neuroscience KIF5B fear learning dendritic spine gephyrin synaptic protein translocation
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Summary:	Kinesin 1 (KIF5) is one major type of motor protein in neurons, but its members’ function in the intact brain remains less studied. Using in vivo two-photon imaging, we find that conditional knockout of Kif5b (KIF5B cKO) in CaMKIIα-Cre-expressing neurons shows heightened turnover and lower stability of dendritic spines in layer 2/3 pyramidal neurons with reduced spine postsynaptic density protein 95 acquisition in the mouse cortex. Furthermore, the RNA-binding protein fragile X mental retardation protein (FMRP) is translocated to the proximity of newly formed spines several hours before the spine formation events in vivo in control mice, but this preceding transport of FMRP is abolished in KIF5B cKO mice. We further find that FMRP is localized closer to newly formed spines after fear extinction, but this learning-dependent localization is disrupted in KIF5B cKO mice. Our findings provide the crucial in vivo evidence that KIF5B is involved in the dendritic targeting of synaptic proteins that underlies dendritic spine plasticity. [Display omitted] •KIF5B regulates synaptic protein composition and turnover of dendritic spines•KIF5B promotes PSD95 gain and maintenance in dendritic spines•KIF5B regulates spine-plasticity-related FMRP localization in baseline condition•KIF5B cKO impairs spine-plasticity-related FMRP localization in fear learning Fok et al. perform intravital imaging to track the translocation of synaptic proteins (PSD95 and gephyrin) and FMRP in dendrites in the mouse frontal cortex. KIF5B is discovered to be necessary for proper PSD95 and FMRP localization in dendrites and activity-dependent dendritic spine plasticity in both baseline and fear learning conditions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2024.113906