Cep215 is essential for morphological differentiation of astrocytes

Kang, Dong‐Hee; Shin, Wonjung; Yoo, Hyunjeong; Kim, Seongjae; Lee, Seongju; Rhee, Kunsoo

doi:10.1038/s41598-020-72728-7

Cited by 3 publications

(3 citation statements)

References 50 publications

(54 reference statements)

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“…It was shown that cFPGS is a cytoskeleton‐microtubule associated protein and is associated with the insoluble cellular fraction involving cytoskeleton and membranes (Stark et al., 2021). On the other hand, Aldh1l1 is also robustly expressed in astrocytes, and this may be correlated with role of Cdk5rap2 in regulating morphological differentiation of astrocytes (Beyer et al., 2021; Cahoy et al., 2008; Kang et al., 2020).…”

Section: Resultsmentioning

confidence: 99%

Proteome changes in autosomal recessive primary microcephaly

Zaqout

Mannaa

Klein

et al. 2022

Annals of Human Genetics

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Background/aim: : Autosomal recessive primary microcephaly (MCPH) is a rare and genetically heterogeneous group of disorders characterized by intellectual disability and microcephaly at birth, classically without further organ involvement. MCPH3 is caused by biallelic variants in the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 gene CDK5RAP2. In the corresponding Cdk5rap2 mutant or Hertwig's anemia mouse model, congenital microcephaly as well as defects in the hematopoietic system, germ cells and eyes have been reported. The reduction in brain volume, particularly affecting gray matter, has been attributed mainly to disturbances in the proliferation and survival of early neuronal progenitors. In addition, defects in dendritic development and synaptogenesis exist that affect the excitation-inhibition balance. Here, we studied proteomic changes in cerebral cortices of Cdk5rap2 mutant mice. Material and methods: : We used large-gel two-dimensional gel (2-DE) electrophoresis to separate cortical proteins. 2-DE gels were visualized by a trained observer on a light box. Spot changes were considered with respect to presence/absence, quantitative variation and altered mobility.

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Section: Resultsmentioning

confidence: 99%

Proteome changes in autosomal recessive primary microcephaly

Zaqout

Mannaa

Klein

et al. 2022

Annals of Human Genetics

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“…The involvement of CDK5RAP2 in cell process formation is also reported in astrocytes. CDK5RAP2 was somehow localized at the cytoplasm of the glial process, and MT nucleation by cytoplasmic CDK5RAP2 is thought to support the growth of glial processes ( Kang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation

Nakamura

Ikeda

Kusayanagi

et al. 2022

IBRO Neuroscience Reports

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“…Based on the single-cell RNAseq from HPA, although the expression of TUBGCP6 has relatively low cell type specificity and brain regional specificity, the highest expression was found in the astrocytes and excitatory neurons of brain (Supplementary Figure 1A). Interestingly, it is well-known that the differentiation of astrocytes is related to brain size (Kang et al, 2020). In addition, the Zika virus can result in the disruption of astrocytic proteins, thereby leading to the featuring symptom of microcephaly (Sher et al, 2019).…”

Section: The Brain-tissue Expression and Frequent Protein-protein Int...mentioning

confidence: 99%

The novel compound heterozygous rare variants may impact positively selected regions of TUBGCP6, a microcephaly associated gene

Ying

Zeng

et al. 2022

Front. Ecol. Evol.

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IntroductionThe microcephaly is a rare and severe disease probably under purifying selection due to the reduction of human brain-size. In contrast, the brain-size enlargement is most probably driven by positive selection, in light of this critical phenotypical innovation during primates and human evolution. Thus, microcephaly-related genes were extensively studied for signals of positive selection. However, whether the pathogenic variants of microcephaly-related genes could affect the regions of positive selection is still unclear.MethodsHere, we conducted whole genome sequencing (WGS) and positive selection analysis.ResultsWe identified novel compound heterozygous variants, p.Y613* and p.E1368K in TUBGCP6, related to microcephaly in a Chinese family. The genotyping and the sanger sequencing revealed the maternal and the paternal origin for the first and second variant, respectively. The p.Y613* occurred before the second and third domain of TUBGCP6 protein, while p.E1368K located within the linker region of the second and third domain. Interestingly, using multiple positive selection analyses, we revealed the potential impacts of these variants on the regions of positive selection of TUBGCP6. The truncating variant p.Y613* could lead to the deletions of two positively selected domains DUF5401 and Spc97_Spc98, while p.E1368K could impose a rare mutation burden on the linker region between these two domains.DiscussionOur investigation expands the list of candidate pathogenic variants of TUBGCP6 that may cause microcephaly. Moreover, the study provides insights into the potential pathogenic effects of variants that truncate or distribute within the positively selected regions.

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Cep215 is essential for morphological differentiation of astrocytes

Cited by 3 publications

References 50 publications

Proteome changes in autosomal recessive primary microcephaly

Proteome changes in autosomal recessive primary microcephaly

An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation

The novel compound heterozygous rare variants may impact positively selected regions of TUBGCP6, a microcephaly associated gene

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