Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects
βPix is a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, which play important roles in dendritic spine morphogenesis by modulating actin cytoskeleton organization. The formation and plasticity of the dendritic spines are essential for normal brain function. Among the altern...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Animal Cells and Systems |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19768354.2024.2448999 |
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| author | Younghee Kwon Seung Joon Lee Yoon Kyung Shin June-Seek Choi Dongeun Park Jung Eun Shin |
| author_facet | Younghee Kwon Seung Joon Lee Yoon Kyung Shin June-Seek Choi Dongeun Park Jung Eun Shin |
| author_sort | Younghee Kwon |
| collection | DOAJ |
| description | βPix is a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, which play important roles in dendritic spine morphogenesis by modulating actin cytoskeleton organization. The formation and plasticity of the dendritic spines are essential for normal brain function. Among the alternatively spliced βPix isoforms, βPix-b and βPix-d are expressed specifically in neurons. Our previous studies using cultured hippocampal neurons identified the roles of βPix-b and βPix-d in spine formation and neurite development, respectively. Here, we analyzed the in vivo role of the neuronal βPix isoforms in brain development and function by using βPix neuronal isoform knockout (βPix-NIKO) mice, in which the expression of the βPix-b and βPix-d isoforms is blocked, while the expression of the ubiquitous βPix-a isoform is maintained. Loss of the neuronal βPix isoforms leads to reduced activity of Rac1 and Cdc42, decreased dendritic complexity and spine density, and increased GluN2B and Ca2+/calmodulin-dependent protein kinase IIα expression in the hippocampus. The defects in neurite development, dendritic spine maturation, and synaptic density in cultured βPix-NIKO hippocampal neurons were rescued by the expression of βPix-b or βPix-d. In behavioral studies, βPix-NIKO mice exhibited robust deficits in novel object recognition and decreased anxiety levels. Our findings suggest that neuronal morphogenetic signaling by the neuronal βPix isoforms contributes to normal behaviors. |
| format | Article |
| id | doaj-art-d022e19865d84ee3b337cc78dc440d1c |
| institution | Kabale University |
| issn | 1976-8354 2151-2485 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Animal Cells and Systems |
| spelling | doaj-art-d022e19865d84ee3b337cc78dc440d1c2025-01-08T19:31:38ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852025-12-01291577110.1080/19768354.2024.2448999Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defectsYounghee Kwon0Seung Joon Lee1Yoon Kyung Shin2June-Seek Choi3Dongeun Park4Jung Eun Shin5School of Biological Sciences, Seoul National University, Seoul, Republic of KoreaSchool of Biological Sciences, Seoul National University, Seoul, Republic of KoreaDepartment of Molecular Neuroscience, College of Medicine, Dong-A University, Busan, Republic of KoreaDepartment of Psychology, Korea University, Seoul, Republic of KoreaSchool of Biological Sciences, Seoul National University, Seoul, Republic of KoreaSchool of Biological Sciences, Seoul National University, Seoul, Republic of KoreaβPix is a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, which play important roles in dendritic spine morphogenesis by modulating actin cytoskeleton organization. The formation and plasticity of the dendritic spines are essential for normal brain function. Among the alternatively spliced βPix isoforms, βPix-b and βPix-d are expressed specifically in neurons. Our previous studies using cultured hippocampal neurons identified the roles of βPix-b and βPix-d in spine formation and neurite development, respectively. Here, we analyzed the in vivo role of the neuronal βPix isoforms in brain development and function by using βPix neuronal isoform knockout (βPix-NIKO) mice, in which the expression of the βPix-b and βPix-d isoforms is blocked, while the expression of the ubiquitous βPix-a isoform is maintained. Loss of the neuronal βPix isoforms leads to reduced activity of Rac1 and Cdc42, decreased dendritic complexity and spine density, and increased GluN2B and Ca2+/calmodulin-dependent protein kinase IIα expression in the hippocampus. The defects in neurite development, dendritic spine maturation, and synaptic density in cultured βPix-NIKO hippocampal neurons were rescued by the expression of βPix-b or βPix-d. In behavioral studies, βPix-NIKO mice exhibited robust deficits in novel object recognition and decreased anxiety levels. Our findings suggest that neuronal morphogenetic signaling by the neuronal βPix isoforms contributes to normal behaviors.https://www.tandfonline.com/doi/10.1080/19768354.2024.2448999Arhgef7guanine nucleotide exchange factordendritic spinesynaptic density |
| spellingShingle | Younghee Kwon Seung Joon Lee Yoon Kyung Shin June-Seek Choi Dongeun Park Jung Eun Shin Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects Animal Cells and Systems Arhgef7 guanine nucleotide exchange factor dendritic spine synaptic density |
| title | Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| title_full | Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| title_fullStr | Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| title_full_unstemmed | Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| title_short | Loss of neuronal βPix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| title_sort | loss of neuronal βpix isoforms impairs neuronal morphology in the hippocampus and causes behavioral defects |
| topic | Arhgef7 guanine nucleotide exchange factor dendritic spine synaptic density |
| url | https://www.tandfonline.com/doi/10.1080/19768354.2024.2448999 |
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