The emerging role of tubulin posttranslational modifications in cilia and ciliopathies
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Biophysics Reports
REVIEW
The emerging role of tubulin posttranslational modifications in cilia and ciliopathies Kai He3, Kun Ling3, Jinghua Hu1,2,3& 1 2 3
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Mayo Translational Polycystic Kidney Diseases Center, Mayo Clinic, Rochester, MN, USA Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
Received: 8 May 2020 / Accepted: 28 June 2020 / Published online: 24 August 2020
Abstract
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 cilia. Dysregulated 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.
Keywords Tubulin posttranslational modifications (PTMs), Cilia, Ciliopathies, Acetylation, Glutamylation, Glycylation
INTRODUCTION Microtubules, assembled from highly conserved a/btubulin heterodimers, are the key cytoskeletal elements for constructing various subcellular organelles. Despite their uniformed structure, microtubules can adapt to a large diversity of functions through spatial–temporal generation of specialized identities. The ‘tubulin code’, which is generated by the expression of different tubulin isotypes and posttranslational modifications (PTMs), confers the dynamic, functional diversity on microtubules (Gadadhar et al. 2017a; Janke 2014; Magiera et al. 2018a, b; Song and Brady 2015). The PTMs not only accumulate on a subset of long-lived microtubules, including those found in the centrosomes, cilia, and axons of neurons, but also on the highly dynamic ones found in mitotic spindle and marginal bands of blood platelets (Gadadhar et al. 2017a; & Correspondence: [email protected] (J. Hu)
Ó The Author(s) 2020
Magiera et al. 2018a, b). In living cells, microtubules can interact with a variety set of microtubule-associated proteins (MAPs), such as microtubule motor proteins, microtubule plus end tracking proteins (?TIPs) and severing enzymes. Mechanistically, PTMs control microtubule functions either by direct alteration of their mechanical properties or by modulating their interactions with other proteins. Many types of PTMs have been discovered on tubulin. Some of them, including acetylation, phosphorylation, and methylation, also occur on non-tubulin substrates. While the others, such as (poly) glutamylation, (poly) glycylation and tyrosination/detyrosination, are mostly
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