Cargando…

Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation

The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene i...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Qi, Wu, Jing, Xia, Yingqian, Cheng, Qing, Zhao, Yinjuan, Zhu, Peixiang, Zhang, Wangling, Zhang, Shihu, Zhang, Lei, Yuan, Yushan, Li, Chaojun, Chen, Guiquan, Xue, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923931/
https://www.ncbi.nlm.nih.gov/pubmed/36782228
http://dx.doi.org/10.1186/s13041-023-01010-4
_version_ 1784887804889661440
author Cheng, Qi
Wu, Jing
Xia, Yingqian
Cheng, Qing
Zhao, Yinjuan
Zhu, Peixiang
Zhang, Wangling
Zhang, Shihu
Zhang, Lei
Yuan, Yushan
Li, Chaojun
Chen, Guiquan
Xue, Bin
author_facet Cheng, Qi
Wu, Jing
Xia, Yingqian
Cheng, Qing
Zhao, Yinjuan
Zhu, Peixiang
Zhang, Wangling
Zhang, Shihu
Zhang, Lei
Yuan, Yushan
Li, Chaojun
Chen, Guiquan
Xue, Bin
author_sort Cheng, Qi
collection PubMed
description The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-023-01010-4.
format Online
Article
Text
id pubmed-9923931
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-99239312023-02-14 Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation Cheng, Qi Wu, Jing Xia, Yingqian Cheng, Qing Zhao, Yinjuan Zhu, Peixiang Zhang, Wangling Zhang, Shihu Zhang, Lei Yuan, Yushan Li, Chaojun Chen, Guiquan Xue, Bin Mol Brain Research The prenylation of proteins is involved in a variety of biological functions. However, it remains unknown whether it plays an important role in the morphogenesis of the cerebellum. To address this question, we generated a mouse model, in which the geranylgeranyl pyrophosphate synthase (Ggps1) gene is inactivated in neural progenitor cells in the developing cerebellum. We report that conditional knockout (cKO) of Ggps1 leads to severe ataxia and deficient locomotion. To identify the underlying mechanisms, we completed a series of cellular and molecular experiments. First, our morphological analysis revealed significantly decreased population of granule cell progenitors (GCPs) and impaired proliferation of GCPs in the developing cerebellum of Ggps1 cKO mice. Second, our molecular analysis showed increased expression of p21, an important cell cycle regulator in Ggps1 cKO mice. Together, this study highlights a critical role of Ggpps-dependent protein prenylation in the proliferation of cerebellar GCPs during cerebellar development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-023-01010-4. BioMed Central 2023-02-13 /pmc/articles/PMC9923931/ /pubmed/36782228 http://dx.doi.org/10.1186/s13041-023-01010-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cheng, Qi
Wu, Jing
Xia, Yingqian
Cheng, Qing
Zhao, Yinjuan
Zhu, Peixiang
Zhang, Wangling
Zhang, Shihu
Zhang, Lei
Yuan, Yushan
Li, Chaojun
Chen, Guiquan
Xue, Bin
Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title_full Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title_fullStr Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title_full_unstemmed Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title_short Disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
title_sort disruption of protein geranylgeranylation in the cerebellum causes cerebellar hypoplasia and ataxia via blocking granule cell progenitor proliferation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923931/
https://www.ncbi.nlm.nih.gov/pubmed/36782228
http://dx.doi.org/10.1186/s13041-023-01010-4
work_keys_str_mv AT chengqi disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT wujing disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT xiayingqian disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT chengqing disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT zhaoyinjuan disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT zhupeixiang disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT zhangwangling disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT zhangshihu disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT zhanglei disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT yuanyushan disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT lichaojun disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT chenguiquan disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation
AT xuebin disruptionofproteingeranylgeranylationinthecerebellumcausescerebellarhypoplasiaandataxiaviablockinggranulecellprogenitorproliferation