A phylogenetic analysis of the CDKL protein family unravels its evolutionary history and supports the Drosophila model of CDKL5 deficiency disorder DOI Creative Commons

María del Carmen Martín-Carrascosa,

Christian Palacios-Martínez,

Máximo Ibo Galindo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 30, 2025

The human CDK-like (CDKL) family of serine‒threonine kinases has five members (CDKL1-5), with a conserved N-terminal kinase domain and variable C-termini. Among these, CDKL5 is particular interest because its involvement in deficiency disorder (CDD), rare epileptic encephalopathy several comorbidities for which there are no specific treatments. Current CDD vertebrate models seizure resistant, could be explained by the genetic background, including leaky expression other CDKLs. Thus, phylogenetic analysis protein would valuable understanding current developing new ones. Our studies revealed that ancestral CDKLs were present all major eukaryotic clades had ciliary/flagellar functions, may have diversified throughout evolution. original CDKL, was likely similar to CDKL5, gave rise remaining through successive duplications. In addition, undergone further gene duplication loss, pattern suggests some functional redundancy among them. A separate study focusing on C-terminal tail suggested this only functionally relevant jawed vertebrates. We developed model Drosophila based downregulation single Cdkl RNAi, results phenotypes those patients, rescued re-expression fly . CDKL proteins contain domain, originally involved ciliary maintenance; therefore, invertebrate organisms can used investigate functions involve aforementioned domain.

Language: Английский

A phylogenetic analysis of the CDKL protein family unravels its evolutionary history and supports the Drosophila model of CDKL5 deficiency disorder DOI Creative Commons

María del Carmen Martín-Carrascosa,

Christian Palacios-Martínez,

Máximo Ibo Galindo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 30, 2025

The human CDK-like (CDKL) family of serine‒threonine kinases has five members (CDKL1-5), with a conserved N-terminal kinase domain and variable C-termini. Among these, CDKL5 is particular interest because its involvement in deficiency disorder (CDD), rare epileptic encephalopathy several comorbidities for which there are no specific treatments. Current CDD vertebrate models seizure resistant, could be explained by the genetic background, including leaky expression other CDKLs. Thus, phylogenetic analysis protein would valuable understanding current developing new ones. Our studies revealed that ancestral CDKLs were present all major eukaryotic clades had ciliary/flagellar functions, may have diversified throughout evolution. original CDKL, was likely similar to CDKL5, gave rise remaining through successive duplications. In addition, undergone further gene duplication loss, pattern suggests some functional redundancy among them. A separate study focusing on C-terminal tail suggested this only functionally relevant jawed vertebrates. We developed model Drosophila based downregulation single Cdkl RNAi, results phenotypes those patients, rescued re-expression fly . CDKL proteins contain domain, originally involved ciliary maintenance; therefore, invertebrate organisms can used investigate functions involve aforementioned domain.

Language: Английский

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