The Role of Tubulin Polymerization-Promoting Protein2 (TPPP2) in Spermatogenesis: A Narrative Review
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PROVIDER: S-EPMC11241133 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:TPPP/p25, a recently identified tubulin polymerization-promoting protein (TPPP), is expressed mainly in myelinating oligodendrocytes of the CNS. Here, we show that TPPP/p25 is strongly upregulated during the differentiation of primary oligodendrocyte cells as well as the CG-4 cell line. The microRNA expression profile of CG-4 cells before and after induction of differentiation was established and revealed differential regulation of a limited subset of microRNAs. miR-206, a microRNA predicted to target TPPP/p25, was not detected in oligodendrocytes. Overexpression of miR-206 led to downregulation of TPPP/p25 resulting in inhibition of differentiation. Transfection of siRNAs against TPPP/p25 also inhibited cell differentiation and promoted cell proliferation, providing evidence for an important role of TPPP/p25 during oligodendrogenesis. These results support an essential role for TPPP/p25 in oligodendrocyte differentiation likely via rearrangement of the microtubule system during the process elongation prior to the onset of myelination.
| S-EPMC2785070 | biostudies-literature
Project description:The eukaryotic cell cycle relies heavily on the mechanical forces vested by the dynamic rearrangement of the microtubule (MT) network. Tubulin Polymerization promoting Protein 1 (TPPP1) alters MT dynamics by driving MT polymerization as well as stabilization, via increasing MT acetylation. It increases MT rigidity, which results in reduced cell proliferation through downregulation of G1/S-phase and mitosis to G1-phase cell cycle transitioning. In this communication, we provide further evidence that TPPP1 may be an important regulator of genomic homeostasis. Our preliminary data show that long-term TPPP1 overexpression reduces cell viability via induction of apoptotic cell death pathways. Moreover, induction of DNA-damage results in increased TPPP1 expression, which is inhibited in the absence of expression of the tumor suppressor p53.
| S-EPMC3925458 | biostudies-literature
Project description:Parkinson's disease (PD) is a progressive neurodegenerative disorder with no known cure. PD is characterized by locomotion deficits, nigrostriatal dopaminergic neuronal loss, mitochondrial dysfunctions and formation of α-Synuclein aggregates. A well-conserved and less understood family of Tubulin Polymerization Promoting Proteins (TPPP) is also implicated in PD and related disorders, where TPPP exists in pathological aggregates in neurons in patient brains. However, there are no in vivo studies on mammalian TPPP to understand the genetics and neuropathology linking TPPP aggregation or neurotoxicity to PD. Recently, we discovered the only Drosophila homolog of human TPPP named Ringmaker (Ringer). Here, we report that adult ringer mutants display progressive locomotor disabilities, reduced lifespan and neurodegeneration. Importantly, our findings reveal that Ringer is associated with mitochondria and ringer mutants have mitochondrial structural damage and dysfunctions. Adult ringer mutants also display progressive loss of dopaminergic neurons. Together, these phenotypes of ringer mutants recapitulate some of the salient features of human PD patients, thus allowing us to utilize ringer mutants as a fly model relevant to PD, and further explore its genetic and molecular underpinnings to gain insights into the role of human TPPP in PD.
| S-EPMC8245532 | biostudies-literature
Project description:Drosophila Ringmaker (Ringer) is homologous to the human Tubulin Polymerization Promoting Proteins (TPPPs) that are implicated in the stabilization and bundling of microtubules (MTs) that are particularly important for neurons and are also implicated in synaptic organization and plasticity. No in vivo functional data exist that have addressed the role of TPPP in synapse organization in any system. Here, we present the phenotypic and functional characterization of ringer mutants during Drosophila larval neuromuscular junction (NMJ) synaptic development. ringer mutants show reduced synaptic growth and transmission and display phenotypic similarities and genetic interactions with the Drosophila homolog of vertebrate Microtubule Associated Protein (MAP)1B, futsch. Immunohistochemical and biochemical analyses show that individual and combined loss of Ringer and Futsch cause a significant reduction in MT loops at the NMJs and reduced acetylated-tubulin levels. Presynaptic over-expression of Ringer and Futsch causes elevated levels of acetylated-tubulin and significant increase in NMJ MT loops. These results indicate that Ringer and Futsch regulate synaptic MT organization in addition to synaptic growth. Together our findings may inform studies on the close mammalian homolog, TPPP, and provide insights into the role of MTs and associated proteins in synapse growth and organization.
| S-EPMC6529516 | biostudies-literature
Project description:Previous studies have demonstrated that ampelopsin (AMP), a type of flavonoid isolated from the stems and leaves of Ampelopsis grossedentata, exhibits anti-cancer activity in various types of cancer. Conversion of AMP into its sodium salt (AMP-Na) conferred enhanced solubility and stability to it. The present study aimed to evaluate the anti-cancer activity of AMP-Na in human lung adenocarcinoma cell lines and to investigate its mechanisms of action. Cell proliferation and viability were assessed by MTT and colony formation assays, and cell migration was determined using a scratch wound healing assay. The cell cycle distribution, apoptosis rate and tubulin immunofluorescence intensity were analyzed using flow cytometry, the cell ultra-microstructure was examined using transmission electron microscopy and the accumulation of tubulin was determined using laser confocal microscopy. The results demonstrated that AMP-Na significantly inhibited the proliferation, clonogenicity and migration of human lung adenocarcinoma cells. Furthermore, AMP-Na induced SPC-A-1 cell apoptosis, and promoted tubulin polymerization. The results suggested that the underlying mechanisms of AMP-Na may involve targeting of microtubules and tubulin polymerization to subsequently disrupt mitosis and induce cell cycle arrest at the S-phase.
| S-EPMC6540484 | biostudies-literature
Project description:The seven most early diverging lineages of the 18 phyla of fungi are the non-terrestrial fungi, which reproduce through motile flagellated zoospores. There are genes/proteins that are present only in organisms with flagellum or cilium. It was suggested that TPPP-like proteins (proteins containing at least one complete or partial p25alpha domain) are among them, and a correlation between the incidence of the p25alpha domain and the eukaryotic flagellum was hypothesized. Of the seven phyla of flagellated fungi, six have been known to contain TPPP-like proteins. Aphelidiomycota, one of the early-branching phyla, has some species (e.g., Paraphelidium tribonematis) that retain the flagellum, whereas the Amoeboaphelidium genus has lost the flagellum. The first two Aphelidiomycota genomes (Amoeboaphelidium protococcorum and Amoeboaphelidium occidentale) were sequenced and published last year. A BLASTP search revealed that A. occidentale does not have a TPPP, but A. protococcorum, which possesses pseudocilium, does have a TPPP. This TPPP is the 'long-type' which occurs mostly in animals as well as other Opisthokonta. P. tribonematis has a 'fungal-type' TPPP, which is found only in some flagellated fungi. These data on Aphelidiomycota TPPP proteins strengthen the correlation between the incidence of p25alpha domain-containing proteins and that of the eukaryotic flagellum/cilium.
| S-EPMC10057920 | biostudies-literature
Project description:Background:Coaches have the potential to support athlete mental wellness, but many are unsure what to do and concerned they may unintentionally engage in behaviours that negatively impact their athletes. Education has the potential to help coaches engage in primary, secondary and tertiary preventive behaviours related to athlete mental health; however, there exists no empirical or consensus basis for specifying the target behaviours that should be included in such education. Objective:The aim of this research was to review extant literature about the role of sport coaches in mental health prevention and promotion, and obtain expert consensus about useful, appropriate and feasible coach behaviours. Design:Modified Delphi methodology with exploration (ie, narrative review) and evaluation phase. Data sources:Twenty-one articles from PubMed, PsycINFO and ProQuest, and grey literature published by prominent sport organisations. Eligibility criteria for selecting studies:All studies were English-language articles that focused on the role of coaches as they relate to (1) culture setting in sport, (2) addressing athlete mental health and (3) providing ongoing support to athletes with mental health concerns. No study design, publication date limits or sport characteristics were applied. Results:The coach's role should include fostering team cultures that support athlete mental health, encouraging care-seeking and supporting athletes currently receiving mental healthcare. Summary/Conclusion:The behaviours specified herein have implications for coach education programme development. This study is the first to use a structured Delphi process to develop specific recommendations about the role coaches can play in supporting athlete mental health.
| S-EPMC7011013 | biostudies-literature
Project description:Tubulin Polymerization Promoting Protein Family Member 3 (TPPP3), a member of the TPPP protein family, has been reported to play important roles in initiation and progression of human cancers. However, the expression and underlying function of TPPP3 in colorectal cancer (CRC) have not yet been fully clarified. In this study, the mRNA and protein levels of TPPP3 in 96 clinical CRC specimens were determined by RT-PCR and immunohistochemistry. The relation between TPPP3 expression and clinicopathologic characteristics and overall survival (OS) were evaluated. Further experiments showed that knockdown of TPPP3 inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro. In addition, TPPP3 silencing resulted in a decrease of angiogenesis and S phase fraction. Thus, our results suggested that TPPP3 played an important role in CRC progress and might serve as novel therapeutic target for CRC treatment.
| S-EPMC5556637 | biostudies-other
Project description:Tau is an intrinsically disordered protein with a central role in the pathology of a number of neurodegenerative diseases. Tau normally functions to stabilize neuronal microtubules, although the mechanism underlying this function is not well understood. Of note is that the interaction between tau and soluble tubulin, which has implications both in understanding tau function as well as its role in disease, is underexplored. Here we investigate the relationship between heterogeneity in tau-tubulin complexes and tau function. Specifically, we created a series of truncated and scrambled tau constructs and characterized the size and heterogeneity of the tau-tubulin complexes formed under nonpolymerizing conditions. Function of the constructs was verified by tubulin polymerization assays. We find that, surprisingly, the pseudo-repeat region of tau, which flanks the core microtubule-binding domain of tau, contributes largely to the formation of large, heterogeneous tau tubulin complexes; additional independent tubulin binding sites exist in repeats two and three of the microtubule binding domain. Of particular interest is that we find positive correlation between the size and heterogeneity of the complexes and rate of tau-promoted microtubule polymerization. We propose that tau-tubulin can be described as a "fuzzy" complex, and our results demonstrate the importance of heterogeneous complex formation in tau function. This work provides fundamental insights into the functional mechanism of tau, and more broadly underscores the relevance of heterogeneous and dynamic complexes in the functions of intrinsically disordered proteins.
| S-EPMC5479049 | biostudies-literature
Project description:During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC(50) values of 3.7+/-0.3 and 2.8+/-0.2 microM, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31+/-0.08 and 0.47+/-0.09 microM, respectively.
| S-EPMC2255563 | biostudies-literature