Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2

Abstract

CDK5RAP2 is one of the primary microcephaly genes that are associated with reduced brain size and mental retardation. We have previously shown that human CDK5RAP2 exists as a full-length form (hCDK5RAP2) or an alternatively spliced variant form (hCDK5RAP2-V1) that is lacking exon 32. The equivalent of hCDK5RAP2-V1 has been reported in rat and mouse but the presence of full-length equivalent hCDK5RAP2 in rat and mouse has not been examined. Here, we demonstrate that rat expresses both a full length and an alternatively spliced variant form of CDK5RAP2 that are equivalent to our previously reported hCDK5RAP2 and hCDK5RAP2-V1, repectively. However, mouse expresses only one form of CDK5RAP2 that is equivalent to the human and rat alternatively spliced variant forms. Knowledge of this expression of different forms of CDK5RAP2 in human, rat and mouse is essential in selecting the appropriate model for studies of CDK5RAP2 and primary microcephaly but our findings further indicate the evolutionary divergence of mouse from the human and rat species.

Assembly and regulation of γ-tubulin complexes

“…In primary keratinocytes, knockdown of NEDD1 was recently claimed to reduce centrosomal localization of γ-tubulin without significantly affecting centrosomal microtubule nucleation [ 54 ], but this interpretation contradicts earlier studies and fails to explain how centrosomes with low levels of γ-tubulin can maintain regular rates of microtubule nucleation [ 24 , 25 ]. The controversy may be partly explained by the observation that different organisms, different cell types or different cellular conditions require different factors for the recruitment and activation of γ-tubulin complexes: for example, NEDD1 is downregulated during differentiation of keratinocytes [ 54 ], and multiple genes encode different CM1 proteins, of which individual ones are expressed under several splice variants in a tissue-specific manner [ 49 , 50 , 56 , 57 ]. Moreover, changes in expression levels or post-translational modifications may alter the interaction between γ TuRCs and regulatory proteins in the same cell throughout the cell cycle, as described for the ratio of MOZART1 bound to γ TuRCs in S. pombe [ 58 ].…”

An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation

“…For example, the alternatively spliced human CDK5RAP2 lacking exon 32 is not expressed in the brain ( Kim et al, 2011 ). The equivalent splicing variation is not even found in mice ( Park et al, 2015 ). Instead, there have been reported two other splicing isoforms in mouse CDK5RAP2.…”