Posttranslational Modifications of Tubulin and Cilia

Włoga, Dorota; Joachimiak, Ewa; Louka, Panagiota; Gaertig, Jacek

doi:10.1101/cshperspect.a028159

Cited by 149 publications

(119 citation statements)

References 146 publications

(206 reference statements)

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“…Localized signaling gradients generated around chromatin and kinetochores (Kalab et al 2002; Weaver and Walczak 2015) likely confer specific topographical identities to midzone MTs in terms of post-translational modifications (Song and Brady 2015; Janke 2014; Wloga et al 2017; Barisic and Maiato 2016) as well as motor and MAP decoration (Gatlin and Bloom 2010; Wang et al 2014; Petry 2016). As a result, MT density, orientation, and accessibility differ with respect to position within the spindle.…”

Section: Discussionmentioning

confidence: 99%

“…Localized signaling gradients generated around chromatin and kinetochores (Kalab, Weis, & Heald, 2002;Weaver and Walczak, 2015) likely confer specific topographical identities to midzone MTs in terms of post-translational modifications (Barisic and Maiato, 2016;Janke, 2014;Song and Brady, 2015;Wloga, Joachimiak, Louka, & Gaertig, 2017) as well as motor and MAP decoration (Gatlin and Bloom, 2010;Petry, 2016;Wang, Brust-Mascher, & Scholey, 2014)…”

Section: Preferential Localization Of Double-handed Constructs To Smentioning

confidence: 99%

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Tau‐based fluorescent protein fusions to visualize microtubules

et al. 2017

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The ability to visualize cytoskeletal proteins and their dynamics in living cells has been critically important in advancing our understanding of numerous cellular processes, including actin- and microtubule-dependent phenomena such as cell motility, cell division, and mitosis. Here we describe a novel set of fluorescent protein fusions designed specifically to visualize microtubules in living systems using fluorescence microscopy. Each fusion contains a fluorescent protein module linked in frame to a modified phospho-deficient version of the microtubule-binding domain of Tau (mTMBD). We found that expressed and purified constructs containing a single mTMBD decorated Xenopus egg extract spindles more homogenously than similar constructs containing the microtubule-binding domain of Ensconsin, suggesting that the binding affinity of mTMBD is minimally affected by localized signaling gradients generated during mitosis. Furthermore, microtubule dynamics were not grossly perturbed by the presence of Tau-based fluorescent protein fusions. Interestingly, the addition of a second mTMBD to the opposite terminus of our construct caused dramatic changes to the spatial localization of probes within spindles. These results support the use of Tau-based fluorescent protein fusions as minimally perturbing tools to accurately visualize microtubules in living systems.

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Section: Discussionmentioning

confidence: 99%

Section: Preferential Localization Of Double-handed Constructs To Smentioning

confidence: 99%

Tau‐based fluorescent protein fusions to visualize microtubules

et al. 2017

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“…Several tubulin PTMs that occur on microtubules like acetylation/ deacetylation, tyrosination/detyrosination, gylcylation/degylcylation, glutamylation/deglutamylation, and polymodifications (such as polyglycylation, polyglutamylation, and polyamination) provide a potential mechanism for the functional specialization of tubulin (reviewed in Janke, 2014;Magiera & Janke, 2014;Magiera, Singh, & Janke, 2018;Song & Brady, 2015;Wloga & Gaertig, 2010;Wloga, Joachimiak, & Fabczak, 2017). Enzymes that catalyze these PTMs revealed key roles of PTMs on microtubules in the regulation of motor protein movement, microtubule-stability, polymerization, and dynamics (reviewed in Magiera & Janke, 2014;Magiera et al, 2018;Song & Brady, 2015;Wloga, Joachimiak, Louka, & Gaertig, 2017;. Tubulin PTMs, and specifically acetylation, detyrosination, and polymodifications have crucial roles in the assembly, maintenance, and function of complex and stable microtubule-based organelles that form the core components of the centrosome such as the centrioles, basal bodies (the protein structure at the base of a cilium or flagellum) and axonemes (the central strand of a cilium or flagellum) (reviewed in Wloga, Joachimiak, Louka, & Gaertig, 2017).…”

Section: Post-translational Modifications (Ptms) Of Microtubules Anmentioning

confidence: 99%

“…Enzymes that catalyze these PTMs revealed key roles of PTMs on microtubules in the regulation of motor protein movement, microtubule-stability, polymerization, and dynamics (reviewed in Magiera & Janke, 2014;Magiera et al, 2018;Song & Brady, 2015;Wloga, Joachimiak, Louka, & Gaertig, 2017;. Tubulin PTMs, and specifically acetylation, detyrosination, and polymodifications have crucial roles in the assembly, maintenance, and function of complex and stable microtubule-based organelles that form the core components of the centrosome such as the centrioles, basal bodies (the protein structure at the base of a cilium or flagellum) and axonemes (the central strand of a cilium or flagellum) (reviewed in Wloga, Joachimiak, Louka, & Gaertig, 2017).…”

Section: Post-translational Modifications (Ptms) Of Microtubules Anmentioning

confidence: 99%

Emerging roles of the centrosome in neuronal development

2020

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The role of the centrosome—a microtubule‐organizing center—in neuronal development has been under scrutiny and is controversial. The function and position of the centrosome have been shown to play an important role in selecting the position of axon outgrowth in cultured neurons and in situ. However, other studies have shown that axonal growth is independent of centrosomal functions. Recent discoveries define the centrosome as an F‐actin organizing organelle in various cell types; thus, giving a whole new perspective to the role of the centrosome in lymphocyte polarity, cell division, and neuronal development. These discoveries compel the need to revisit centrosomal functions by investigating the fundamental mechanisms that regulate centrosomal F‐actin remodeling during neuronal differentiation and polarization. In this review, we summarize the up‐to‐date knowledge regarding the function of the centrosome in neuronal differentiation. We put special emphasis on recent findings describing the centrosome as an F‐actin organizing center. Additionally, with the available data regarding centrosome, microtubules and F‐actin organization, we provide a model on how centrosomal F‐actin could be modulating neuronal differentiation and polarity.

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“…PTMs of α -tubulin have been linked to a variety of human pathogenic phenotypes (Magiera et al, 2018). Axonemal microtubules (MTs) are a common target for several PTMs, and the amount of PTMs increases during maturation of the cilium, distinguishing mature cilia from assembling/immature cilia (Wloga et al, 2017). Stable MTs are marked by acetylation, and axonemal MTs are a common target for acetylation contributing to ciliogenesis and ciliary mechanosensing (Aguilar et al, 2014;Shida et al, 2010).…”

Section: Fads Fibroblasts Have Shorter Primary Ciliamentioning

confidence: 99%

Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts

Jühlen

Martinelli

Vinci

et al. 2019

Preprint

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Ciliopathies are clinical disorders of the primary cilium with widely recognized phenotypic and genetic heterogeneity. Here we found that impaired ciliogenesis in fibroblasts derived from individuals with fetal akinesia deformation sequence (FADS).FADS refers to a broad spectrum of neuromuscular disorders arising from impaired fetal movement. We show that cells derived from two FADS individuals, one with an unknown genetic cause and one with bi-allelic pathogenic variants in RAPSN, have shorter and less primary cilia (PC), in association with alterations in posttranslational modifications in α -tubulin. Similarly, siRNA-mediated depletion of two known FADS proteins, the scaffold protein rapsyn and the nucleoporin NUP88, resulted in defective PC formation. Consistent with a role in ciliogenesis, rapsyn and NUP88 localized to centrosomes and PC. By proximity-ligation assays, we show that rapsyn and NUP88 are interacting and that both proteins are connecting to all three tubulin isoforms (α, ß, and γ ). The rapsyn-NUP88 interface, as well as their contact to microtubules, is perturbed in the examined FADS cells, similarly to their contact to microtubules. We suggest that the perturbed rapsyn-NUP88-tubulin interface leads to defects in PC formation and that defective ciliogenesis contributes to the pleiotropic defects seen in FADS.

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Posttranslational Modifications of Tubulin and Cilia

Cited by 149 publications

References 146 publications

Tau‐based fluorescent protein fusions to visualize microtubules

Tau‐based fluorescent protein fusions to visualize microtubules

Emerging roles of the centrosome in neuronal development

Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts

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