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The emerging role of tubulin posttranslational modifications in cilia and ciliopathies

Biophysics Reports 2020年第4期6卷 89-104页

作者： Kai He Kun Ling Jinghua Hu Department of Biochemistry and Molecular Biology Mayo Clinic Division of Nephrology and Hypertension Mayo Clinic Mayo Translational Polycystic Kidney Diseases Center Mayo Clinic

Tubulin posttranslational modifications(PTMs) add ‘ tubulin code”” to generate functional diversities of microtubules. Several types of tubulin PTMs accumulate on axonemes and basal bodies of cilia,including acetylation, glutamylation, glycylation and detyrosination. Among them, glutamylation, glycylation and detyrosination are mostly enriched in the B-tubules, whereas acetylation occurs on both Aand B-tubule of the microtubule doublets in a similar level. Recent studies indicate that tubulin PTMs are critical for the fine tuning of assembly/disassembly, maintenance, motility, and signaling of *** tubulin PTMs are strongly implicated in human disorders including ciliopathies and neuron degeneration. Here, we review the current understanding how tubulin PTMs regulate cilia formation and function, and their relevance to human health.

关键词： Tubulin posttranslational modifications (PTMs) Cilia ciliopathies Acetylation Glutamylation Glycylation

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New insights into the roles for DYRK family in mammalian development and congenital diseases

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Genes & Diseases 2023年第3期10卷 758-770页

作者： Saishu Yoshida Kiyotsugu Yoshida Department of Biochemistry The Jikei University School of MedicineMinato-kuTokyo 1058461Japan

The dual-specificity tyrosine-regulated kinase (DYRK) family is evolutionarily conserved from invertebrate to mammals. DYRKs regulate cell proliferation, apoptosis, survival, and differentiation by modifying the protein activation state, cellular localization, and turnover. In contrast to several studies in cellular models, the available evidence regarding the in vivo roles of DYRKs in mammalian development is limited. This review summarizes the in vivo studies on Dyrks which provide insight into their roles in mammalian tissue development and congenital diseases. In vivo evidence obtained using knockout and genetically modified animals helps to understand and develop novel clinical therapies and drug for human congenital diseases, such as Down syndrome and neuronal disorders (associated with DYRK1A) and skeletal ciliopathies (associated with DYRK2).

关键词： ciliopathies Development Down syndr ome DYRKS Embryogenesis

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