Post-translational modifications of microtubule- and growth-associated proteins in nerve regeneration and neuropathy

1995 ◽  
Vol 23 (1) ◽  
pp. 76-80 ◽  
Author(s):  
W. G. McLean ◽  
R. E. Roberts ◽  
F. H. Mullins
Keyword(s):  
Nerve Regeneration ◽  
Post Translational Modifications ◽  
Associated Proteins

Post-ovulatory ageing of mouse oocytes affects the distribution of specific spindle-associated proteins and Akt expression levels

2014 ◽  
Vol 26 (4) ◽  
pp. 562 ◽  
Author(s):  
Sandra Cecconi ◽  
Gianna Rossi ◽  
Hamid Deldar ◽  
Valerio Cellini ◽  
Felice Patacchiola ◽  
...  
Keyword(s):  
Histone H3 ◽  
Meiotic Spindle ◽  
Post Translational Modifications ◽  
Expression Levels ◽  
Acetylated Tubulin ◽  
Protein Levels ◽  
Histone 3 ◽  
Phosphorylated Akt ◽  
Associated Proteins

The aim of this study has been to determine the effects of in vivo post-ovulatory ageing (POA) on the distribution of spindle-associated proteins, histone H3/H4 post-translational modifications and on v-akt murine thymoma viral oncogene homolog 1 (Akt) expression levels. To this end, oocytes were retrieved 13, 29 and 33 h after human chorionic gonadotrophin (hCG) treatment. The presence and distribution at the meiotic spindle of acetylated tubulin, γ-tubulin, polo kinase-1 and Ser473/Thr308 phosphorylated Akt (pAkt) as well as histone H3 and H4 acetylation and phosphorylation levels were assayed via immunofluorescence. Akt expression levels were determined via reverse transcription–polymerase chain reaction and western blotting analyses. Spindles from oocytes recovered 13 h and 29 h after hCG treatment showed similar levels of acetylated tubulin but ageing induced: (1) translocation of γ-tubulin from spindle poles to microtubules, (2) absence of Thr308- and Ser473-pAkt in 76% and 30% of oocytes, respectively, and (3) a significant reduction in phosphorylation levels of serine 10 on histone 3. At 29 h, a significant decrease in Akt mRNA, but not in pAkt or Akt protein levels, was recorded. By contrast, protein content significantly decreased 33 h after hCG. We conclude that POA impairs oocyte viability and fertilisability by altering the expression levels and spindle distribution of proteins that are implicated in cell survival and chromosome segregation. Together, these events could play a role in oocyte apoptosis.

scholarly journals Proteomic Identification of an Endogenous Synaptic SUMOylome in the Developing Rat Brain

2021 ◽  
Vol 14 ◽  
Author(s):  
Marie Pronot ◽  
Félicie Kieffer ◽  
Anne-Sophie Gay ◽  
Delphine Debayle ◽  
Raphaël Forquet ◽  
...  
Keyword(s):  
Subcellular Fractionation ◽  
Mass Spectrometry Analysis ◽  
Mammalian Brain ◽  
Synaptic Organization ◽  
Post Translational Modifications ◽  
Spectrometry Analysis ◽  
Functional Changes ◽  
Neuronal Communication ◽  
Associated Proteins ◽  
And Function

Synapses are highly specialized structures that interconnect neurons to form functional networks dedicated to neuronal communication. During brain development, synapses undergo activity-dependent rearrangements leading to both structural and functional changes. Many molecular processes are involved in this regulation, including post-translational modifications by the Small Ubiquitin-like MOdifier SUMO. To get a wider view of the panel of endogenous synaptic SUMO-modified proteins in the mammalian brain, we combined subcellular fractionation of rat brains at the post-natal day 14 with denaturing immunoprecipitation using SUMO2/3 antibodies and tandem mass spectrometry analysis. Our screening identified 803 candidate SUMO2/3 targets, which represents about 18% of the synaptic proteome. Our dataset includes neurotransmitter receptors, transporters, adhesion molecules, scaffolding proteins as well as vesicular trafficking and cytoskeleton-associated proteins, defining SUMO2/3 as a central regulator of the synaptic organization and function.

scholarly journals Microtubule polyglutamylation is important for regulating cytoskeletal architecture and motility in Trypanosoma brucei

2020 ◽  
Vol 133 (18) ◽  
pp. jcs248047 ◽  
Author(s):  
Jana Jentzsch ◽  
Adal Sabri ◽  
Konstantin Speckner ◽  
Gertrud Lallinger-Kube ◽  
Matthias Weiss ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Dynamic Behaviour ◽  
Cell Movement ◽  
Post Translational Modifications ◽  
Life Cycle Stages ◽  
Associated Proteins ◽  
Flagellar Axoneme

ABSTRACTThe shape of kinetoplastids, such as Trypanosoma brucei, is precisely defined during the stages of the life cycle and governed by a stable subpellicular microtubule cytoskeleton. During the cell cycle and transitions between life cycle stages, this stability has to transiently give way to a dynamic behaviour to enable cell division and morphological rearrangements. How these opposing requirements of the cytoskeleton are regulated is poorly understood. Two possible levels of regulation are activities of cytoskeleton-associated proteins and microtubule post-translational modifications (PTMs). Here, we investigate the functions of two putative tubulin polyglutamylases in T. brucei, TTLL6A and TTLL12B. Depletion of both proteins leads to a reduction in tubulin polyglutamylation in situ and is associated with disintegration of the posterior cell pole, loss of the microtubule plus-end-binding protein EB1 and alterations of microtubule dynamics. We also observe a reduced polyglutamylation of the flagellar axoneme. Quantitative motility analysis reveals that the PTM imbalance correlates with a transition from directional to diffusive cell movement. These data show that microtubule polyglutamylation has an important role in regulating cytoskeletal architecture and motility in the parasite T. brucei.This article has an associated First Person interview with the first author of the paper.

scholarly journals Cilium structure, assembly, and disassembly regulated by the cytoskeleton

2018 ◽  
Vol 475 (14) ◽  
pp. 2329-2353 ◽  
Author(s):  
Mary Mirvis ◽  
Tim Stearns ◽  
W. James Nelson
Keyword(s):  
Cell Polarity ◽  
Control Cell ◽  
Microtubule Dynamics ◽  
Function Structure ◽  
Post Translational Modifications ◽  
The Core ◽  
Associated Proteins ◽  
Differentiation And Proliferation ◽  
Structure Assembly ◽  
Cilium Function

The cilium, once considered a vestigial structure, is a conserved, microtubule-based organelle critical for transducing extracellular chemical and mechanical signals that control cell polarity, differentiation, and proliferation. The cilium undergoes cycles of assembly and disassembly that are controlled by complex inter-relationships with the cytoskeleton. Microtubules form the core of the cilium, the axoneme, and are regulated by post-translational modifications, associated proteins, and microtubule dynamics. Although actin and septin cytoskeletons are not major components of the axoneme, they also regulate cilium organization and assembly state. Here, we discuss recent advances on how these different cytoskeletal systems­ affect cilium function, structure, and organization.

scholarly journals Mitotic Acetylation of Microtubules Promotes Centrosomal PLK1 Recruitment and Is Required to Maintain Bipolar Spindle Homeostasis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1859
Author(s):  
Sylvia Fenosoa Rasamizafy ◽  
Claude Delsert ◽  
Gabriel Rabeharivelo ◽  
Julien Cau ◽  
Nathalie Morin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitotic Spindle ◽  
Mitotic Progression ◽  
Post Translational Modifications ◽  
Microtubule Associated Proteins ◽  
Mitotic Kinase ◽  
Tubulin Acetylation ◽  
Associated Proteins ◽  
Spindle Microtubules ◽  
Bipolar Spindles

Tubulin post-translational modifications regulate microtubule properties and functions. Mitotic spindle microtubules are highly modified. While tubulin detyrosination promotes proper mitotic progression by recruiting specific microtubule-associated proteins motors, tubulin acetylation that occurs on specific microtubule subsets during mitosis is less well understood. Here, we show that siRNA-mediated depletion of the tubulin acetyltransferase ATAT1 in epithelial cells leads to a prolonged prometaphase arrest and the formation of monopolar spindles. This results from collapse of bipolar spindles, as previously described in cells deficient for the mitotic kinase PLK1. ATAT1-depleted mitotic cells have defective recruitment of PLK1 to centrosomes, defects in centrosome maturation and thus microtubule nucleation, as well as labile microtubule-kinetochore attachments. Spindle bipolarity could be restored, in the absence of ATAT1, by stabilizing microtubule plus-ends or by increasing PLK1 activity at centrosomes, demonstrating that the phenotype is not just a consequence of lack of K-fiber stability. We propose that microtubule acetylation of K-fibers is required for a recently evidenced cross talk between centrosomes and kinetochores.

scholarly journals Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in C. elegans

2020 ◽  
Author(s):  
Aya Sato-Carlton ◽  
Chihiro Nakamura-Tabuchi ◽  
Xuan Li ◽  
Hendrik Boog ◽  
Madison K Lehmer ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Post Translational Modifications ◽  
C Elegans ◽  
Phosphorylated Proteins ◽  
C Terminus ◽  
The Hierarchical Structure ◽  
Associated Proteins ◽  
Domain Protein

AbstractIn the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is that used by the nematode Caenorhabditis elegans, where upon division of the chromosome into two segments or arms by the single off-center crossover, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the short or long arm, where they affect the timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved “closure motif” region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover recombination sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

Post-translational modifications and stabilization of microtubules regulate transport of viral factors during infections

2021 ◽  
Vol 49 (4) ◽  
pp. 1735-1748
Author(s):  
Silvia Requena ◽  
Francisco Sánchez-Madrid ◽  
Noa B. Martín-Cófreces
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Building Blocks ◽  
Cell Types ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Associated Proteins ◽  
The Stability ◽  
Different Characteristics ◽  
Β Tubulin

Tubulin post-translational modifications (PTMs) constitute a source of diversity for microtubule (MT) functions, in addition to the different isotypes of α and β-tubulin acting as building blocks of MTs. Also, MT-associated proteins (MAPs) confer different characteristics to MTs. The combination of all these factors regulates the stability of these structures that act as rails to transport organelles within the cell, facilitating the association of motor complexes. All these functions are involved in crucial cellular processes in most cell types, ranging from spindle formation in mitosis to the defense against incoming cellular threats during phagocytosis mediated by immune cells. The regulation of MT dynamics through tubulin PTMs has evolved to depend on many different factors that act in a complex orchestrated manner. These tightly regulated processes are particularly relevant during the induction of effective immune responses against pathogens. Viruses have proved not only to hijack MTs and MAPs in order to favor an efficient infection, but also to induce certain PTMs that improve their cellular spread and lead to secondary consequences of viral processes. In this review, we offer a perspective on relevant MT-related elements exploited by viruses.

scholarly journals Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans

PLoS Genetics ◽  
2020 ◽  
Vol 16 (11) ◽  
pp. e1008968
Author(s):  
Aya Sato-Carlton ◽  
Chihiro Nakamura-Tabuchi ◽  
Xuan Li ◽  
Hendrik Boog ◽  
Madison K. Lehmer ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Synaptonemal Complex ◽  
Post Translational Modifications ◽  
Phosphorylated Proteins ◽  
C Terminus ◽  
The Hierarchical Structure ◽  
Associated Proteins ◽  
Domain Protein

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved “closure motif” region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

scholarly journals Oxygen-dependent changes in HIF binding partners and post-translational modifications regulate stability and transcriptional activity

2020 ◽  
Author(s):  
Leonard Daly ◽  
Philip J. Brownridge ◽  
Violaine Sée ◽  
Claire E. Eyers
Keyword(s):  
Transcriptional Activity ◽  
Evolutionary Analysis ◽  
Post Translational Modification ◽  
Low Oxygen ◽  
Post Translational Modifications ◽  
Functional Roles ◽  
Binding Partners ◽  
Associated Proteins ◽  
The Stability

AbstractAdaption of cells to low oxygen environments is an essential process mediated in part by the Hypoxia Inducible Factors (HIFs). Like other transcription factors, the stability and transcriptional activity of HIFs, and consequently the hypoxic response, are regulated by post-translational modification (PTM) and changes in biomolecular interactions. However, our current understanding of PTM-mediated regulation of HIFs is primarily based on in vitro protein fragment-based studies, with validation typically having been conducted by in cellulo fragment expression and hypoxia mimicking drugs. Consequently, we still lack an understanding of true oxygen deprivation signaling via HIFα. Using an immunoprecipitation-based, mass spectrometry approach, we characterize the regulation of in cellulo expressed full-length HIF-1α and HIF-2α, in terms of both PTM and binding partners, in response to normoxia (21% oxygen) and hypoxia (1% oxygen). These studies revealed that a change in oxygen tension significantly alters the complexity and composition of HIF-α protein interaction networks, with HIF-2α in particular having an extended hypoxia-induced interactome, most notably with mitochondrial-associated proteins. Both HIFα isoforms are heavily covalently modified: we define ~40 different sites of PTM on each of HIF-1α and HIF-2α, comprising 13 different PTM types, including multiple cysteine modifications and a highly unusual phosphocysteine. Over 80% of the PTMs identified are novel, and approximately half exhibit oxygen-dependency under these conditions. Combined with domain and evolutionary analysis of >225 vertebrate species, we validate Ser31 phosphorylation on HIF-1α as a regulator of transcription, and propose functional roles for Thr406, Thr528 and Ser581 on HIF-2α.

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