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Mammalian Spermatozoa
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Various studies have shown that multiple forms of α- and β-tubulins exist in the same organism and even the same tissue,14-17 the testis being no exception.18-20 Unique β- and α-tubulin genes have been shown to be expressed in the testis.21-25 In Drosophila, testis-specific β2-tublin mutations do not alter the early mitotic divisions but abrogate subsequent mi-crotubule-mediated events, including meiosis, and assembly of the axoneme.21-23 Pratt et al.25 have identified a novel cα2-tubulin in chicken testes containing a nonconservative carboxy terminus sequence which lacks a terminal tyrosine and thus probably does not participate in the usual cycle of tyrosination/detyrosination.26 Because there is a preferential association of detyrosinated tubulin subunits with stable microtubules of centrioles and primary cilia in cultured fibroblasts and of axonemes and basal bodies in sperm and tracheal cells,27 Pratt et al.25 suggest that the ca2-tubulin may be involved in the assembly of stable microtubules in the chicken spermatid manchette and axoneme. The most compelling evidence for a specific testicular α-tubulin in mammals, which may take part in the construction of the manchette or axoneme (events which occur solely in spermiogenesis), is the isolation of a cDNA clone from mouse testis which is exclusively expressed in postmeiotic testicular cells.24,28-29
Translation and Post-Translational Modifications During Aging
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
Detyrosination of microtubules169 affecting the cytoskeletal organization and many other cellular functions may also be important during aging. Furthermore, the roles of chaperones in protein folding and conformational organization170 have yet to be studied in relation to the aging process. However, ubiquitin marking of proteins for degradation and ubiquitin-mediated proteolysis do not decline during aging, since no change was found in the levels of ubiquitin mRNA and ubiquitin pools in aging human fibroblasts in protein degradation.171
Tubulin inhibitors as novel anticancer agents: an overview on patents (2013-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Kashif Haider, Shaik Rahaman, M Shahar Yar, Ahmed Kamal
Microtubules are highly dynamic structures whose regulation is critical for cell division, polarity, and neuronal differentiation. These are affected easily by the external or intrinsic changes leading to the caseation of the cell cycle and cell death or apoptosis. Several proteins regulate microtubule dynamics by posttranslational modifications of the tubulin dimers such as acetylation, detyrosination, and poly-glycylation. Changes at β-tubulins (the plus ends) can affect both dynamics and function of microtubules.
Molecular mechanisms governing axonal transport: a C. elegans perspective
Published in Journal of Neurogenetics, 2020
Amruta Vasudevan, Sandhya P. Koushika
Post-translational modifications (PTMs) such as acetylation, polyglutamylation and detyrosination are markers for stable microtubules (Janke & Chloë Bulinski, 2011), and are often found enriched in axons as compared to dendrites (Hammond, Huang, et al., 2010). PTMs have been reported to regulate the motility of microtubule-dependent motors such as Kinesin-1 (Balabanian, Berger, & Hendricks, 2017), and organelles such as mitochondria in cultured neurons (Magiera et al., 2018).
Emerging gene therapy products for RPGR-associated X-linked retinitis pigmentosa
Published in Expert Opinion on Emerging Drugs, 2022
Cristina Martinez-Fernandez de la Camara, Jasmina Cehajic-Kapetanovic, Robert E. MacLaren
The activation of the proteins that constitute the regulatory network in the connecting cilia, and the large diversity of functions that these develop are mechanistically controlled by post-translational modifications. Specialized functions of microtubule-associated proteins have been related to glutamylation, glycylation, and tyrosination/detyrosination [78]. Glutamylation, the addition of glutamate side chains on glutamate residues catalyzed by Tubulin Tyrosine Ligase-like (TTLL) enzymes, contributes to the stabilization of microtubules and regulates the recruitment and activity of microtubule-interacting proteins [79]. RPGRORF15 is a glutamylation substrate [69,80]. Exon ORF15 is translated into a glutamic acid-glycine rich domain comprising G and E residues as repeat-like sequence such as ‘EEEGEGEGE'. This region can be considered as an intrinsically disordered region since it contains a high proportion of glutamic acid residues (60.1%) which could prevent a protein domain to mediate cooperative folding. The computation of various physical and chemical parameters of the ORF15 region determines that this unique sequence has an instability index of 87.52, which classifies this domain as unstable [81]. But what appears to be a disordered region with unstable structure, could be providing specialized functional advantages [82]. TTLL5 enzyme, expressed in rod and cone photoreceptors, interacts with the basic domain of RPGRORF15 and catalyzes the addition of glutamates to the 11 consensus motifs within the ORF15. The addition of negative charges to the ORF15 region might affect the stabilization of the RPGRORF15 protein, and the integrity of the RPGRORF15 containing protein complexes in the connecting cilia [69,83]. To date, there is no evidence that supports that RPGRORF15 can preserve fully its function with a reduced level of glutamylation and it has been suggested that a complete or partial lack of glutamylation may compromise RPGRORF15 function [80]. Indeed, loss-of-function variants in TTLL5, that lead to a lack of glutamylation, have been identified as a cause of recessive retinal dystrophy, similar to RPGR deficiency [49].