CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development
The cytosolic carboxypeptidase (CCP) 1 protein, encoded by <i>CCP1</i>, is expressed in cerebellar Purkinje cells (PCs). The dysfunction of CCP1 protein (caused by <i>CCP1</i> point mutation) and the deletion of CCP1 protein (caused by <i>CCP1</i> gene knockout) a...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5335 |
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| author | Bo Pang Asuka Araki Li Zhou Hirohide Takebayashi Takayuki Harada Kyuichi Kadota |
| author_facet | Bo Pang Asuka Araki Li Zhou Hirohide Takebayashi Takayuki Harada Kyuichi Kadota |
| author_sort | Bo Pang |
| collection | DOAJ |
| description | The cytosolic carboxypeptidase (CCP) 1 protein, encoded by <i>CCP1</i>, is expressed in cerebellar Purkinje cells (PCs). The dysfunction of CCP1 protein (caused by <i>CCP1</i> point mutation) and the deletion of CCP1 protein (caused by <i>CCP1</i> gene knockout) all lead to the degeneration of cerebellar PCs, which leads to cerebellar ataxia. Thus, two <i>CCP1</i> mutants (i.e., Ataxia and Male Sterility [AMS] mice and Nna1 knockout [KO] mice) are used as disease models. We investigated the cerebellar CCP1 distribution in wild-type (WT), AMS and Nna1 KO mice on postnatal days (P) 7–28 to investigate the differential effects of CCP protein deficiency and disorder on cerebellar development. Immunohistochemical and immunofluorescence studies revealed significant differences in the cerebellar CCP1 expression in WT and mutant mice of P7 and P15, but no significant difference between AMS and Nna1 KO mice. Electron microscopy showed slight abnormality in the nuclear membrane structure of PCs in the AMS and Nna1 KO mice at P15 and significant abnormality with depolymerization and fragmentation of microtubule structure at P21. Using two <i>CCP1</i> mutant mice strains, we revealed the morphological changes of PCs at postnatal stages and indicated that CCP1 played an important role in cerebellar development, most likely via polyglutamylation. |
| first_indexed | 2024-03-11T06:26:38Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:38Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f3ecb96cab7845debabd8c77df8700b32023-11-17T11:32:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246533510.3390/ijms24065335CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar DevelopmentBo Pang0Asuka Araki1Li Zhou2Hirohide Takebayashi3Takayuki Harada4Kyuichi Kadota5Department of Organ Pathology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo 693-8501, JapanPathology Division, Shimane University Hospital, Izumo 693-8501, JapanDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, JapanDivision of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, JapanDepartment of Organ Pathology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo 693-8501, JapanPathology Division, Shimane University Hospital, Izumo 693-8501, JapanThe cytosolic carboxypeptidase (CCP) 1 protein, encoded by <i>CCP1</i>, is expressed in cerebellar Purkinje cells (PCs). The dysfunction of CCP1 protein (caused by <i>CCP1</i> point mutation) and the deletion of CCP1 protein (caused by <i>CCP1</i> gene knockout) all lead to the degeneration of cerebellar PCs, which leads to cerebellar ataxia. Thus, two <i>CCP1</i> mutants (i.e., Ataxia and Male Sterility [AMS] mice and Nna1 knockout [KO] mice) are used as disease models. We investigated the cerebellar CCP1 distribution in wild-type (WT), AMS and Nna1 KO mice on postnatal days (P) 7–28 to investigate the differential effects of CCP protein deficiency and disorder on cerebellar development. Immunohistochemical and immunofluorescence studies revealed significant differences in the cerebellar CCP1 expression in WT and mutant mice of P7 and P15, but no significant difference between AMS and Nna1 KO mice. Electron microscopy showed slight abnormality in the nuclear membrane structure of PCs in the AMS and Nna1 KO mice at P15 and significant abnormality with depolymerization and fragmentation of microtubule structure at P21. Using two <i>CCP1</i> mutant mice strains, we revealed the morphological changes of PCs at postnatal stages and indicated that CCP1 played an important role in cerebellar development, most likely via polyglutamylation.https://www.mdpi.com/1422-0067/24/6/5335Purkinje cells (PCs)CCP1/Nna1/<i>AGTPBP1</i>Ataxia and Male Sterility (AMS)polyglutamylationneurodegenerative |
| spellingShingle | Bo Pang Asuka Araki Li Zhou Hirohide Takebayashi Takayuki Harada Kyuichi Kadota CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development International Journal of Molecular Sciences Purkinje cells (PCs) CCP1/Nna1/<i>AGTPBP1</i> Ataxia and Male Sterility (AMS) polyglutamylation neurodegenerative |
| title | CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development |
| title_full | CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development |
| title_fullStr | CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development |
| title_full_unstemmed | CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development |
| title_short | CCP1, a Regulator of Tubulin Post-Translational Modifications, Potentially Plays an Essential Role in Cerebellar Development |
| title_sort | ccp1 a regulator of tubulin post translational modifications potentially plays an essential role in cerebellar development |
| topic | Purkinje cells (PCs) CCP1/Nna1/<i>AGTPBP1</i> Ataxia and Male Sterility (AMS) polyglutamylation neurodegenerative |
| url | https://www.mdpi.com/1422-0067/24/6/5335 |
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