Novel Alternative Splice Variants of Mouse Cdk5rap2

Abstract

Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice.

Microtubule nucleation by γ-tubulin complexes and beyond

“…This suggests that similar regulatory regions may exist in other CM1-domain proteins, but more work is needed to test these models and reveal any conservation across species. Given the recent findings that different Cnn isoforms bind differently to γ-TuRCs [38] and recruit γ-TuRCs to different MTOCs [81], it will be important to explore potential isoform differences in other γ-TuRC-tethering proteins and in Cnn homologues in different species, particularly as different CDK5RAP2 isoforms do exist [109–111]. It is likely that a combination of phosphorylation and isoform differences contributes to the tight spatiotemporal regulation of γ-TuRC recruitment and activation.…”

Identification of the Glucose Metabolism Biomarkers of NASH: Weighted Gene Co-Expression Network Analysis

“…CDK5RAP3 is a protein-coding gene in the long arm of chromosome 20 [19]. CDK5RAP3 has a variety of transcriptional variants, forming different isoforms [20]. Diseases associated with CDK5RAP3 include renal cancer, hepatocellular carcinoma and diabetes [21,22,23].…”

An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation

“…Instead, there have been reported two other splicing isoforms in mouse CDK5RAP2. One is carrying additional axon 3a between exon 3 and exon 4 ( Kraemer et al, 2015 ). This inclusion causes a frameshift at the beginning of the CM1 domain.…”

“…This inclusion causes a frameshift at the beginning of the CM1 domain. The second isoform is a transcript from an alternative start site before exon 7 ( Kraemer et al, 2015 ). This variant encodes shorter CDK5RAP2 protein lacking the N-terminus CM1 domain.…”