Zinc-induced structural changes of the disordered tppp/p25 inhibits its degradation by the proteasome

Lehotzky, Attila; Oláh, Judit; Szunyogh, Sándor; Szabó, Adél; Berki, Tímea; Ovádi, Judit

doi:10.1016/j.bbadis.2014.10.015

Cited by 10 publications

(21 citation statements)

References 51 publications

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“…The spontaneous formation of the intermolecular covalent bridges at room temperature above 10 μM TPPP/p25 concentration can ensure the detection of dimers even by SDS/PAGE4. However, it is important to emphasize that TPPP/p25 dimers were detected in our lab, but not in Skoufias’s lab, by sandwich ELISA, isothermal titration calorimetry and size exclusion gel chromatography as well48.…”

Section: Discussionmentioning

confidence: 67%

“…Our sandwich ELISA assay using mouse monoclonal TPPP/p25 antibody9 (mAb) labelled with and without biotin exclusively detects dimeric/oligomeric forms of TPPP/p25 in solution independently whether they are stabilized by disulphide bridges or not8.…”

Section: Resultsmentioning

confidence: 99%

“…In this paper we refer to a couple of data reported previously458; in addition, new sets of experiments have also been performed that allowed us to suggest a plausible mechanism for the role of the unstructured N- and C-termini of TPPP/p25 in the dimer-derived MT bundling. Our previous electron microscopic studies underlined that the MTs are cross-linked by TPPP/p25, formed bundles of 25–26 nm in diameter consisting of dozens of MTs decorated by rows of tiny projections and dense particles with a periodicity of about 16 nm were observed211.…”

Section: Discussionmentioning

confidence: 99%

“…have provided evidence for concentration-dependent dimerization of TPPP/p25 in the absence of MTs4, however, it is promoted by the presence of ligands such as GTP4 and the bivalent zinc ion8. We have also established the role of intermolecular disulphide bridges in the stabilization of the dimers4, and that in the presence of dithioerythritol (DTE) (its epimer, DTT was used in the commented paper) the detection of the dimer forms is ambiguous48. In the experiments presented in Skoufias’s paper1, DTT (1 mM) is present in the TPPP/p25 solutions including the stored stock solutions and the solutions used for the binding and polymerization assays.…”

mentioning

confidence: 99%

“…In addition, we detected the dimeric form by other approaches as well such as sandwich enzyme-linked immunosorbent assay (ELISA)8, size exclusion gel chromatography4 and isothermal titration calorimetry4. Now we have performed sandwich ELISA experiment with the N- and/or C-terminal free forms as earlier with the full length protein to establish the role of the unstructured terminal segments in the dimerization of the TPPP/p25.…”

mentioning

confidence: 99%

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Further evidence for microtubule-independent dimerization of TPPP/p25

Oláh

Szénási

Szunyogh

et al. 2017

Sci Rep

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Tubulin Polymerization Promoting Protein (TPPP/p25) is a brain-specific disordered protein that modulates the dynamics and stability of the microtubule network by its assembly promoting, cross-linking and acetylation enhancing activities. In normal brain it is expressed primarily in differentiated oligodendrocytes; however, at pathological conditions it is enriched in inclusions of both neurons and oligodendrocytes characteristic for Parkinson’s disease and multiple system atrophy, respectively. The objective of this paper is to highlight a critical point of a recently published Skoufias’s paper in which the crucial role of the microtubules in TPPP/p25 dimerization leading to microtubule bundling was suggested. However, our previous and present data provide evidence for the microtubule-independent dimerization of TPPP/p25 and its stabilization by disulphide bridges. In addition, our bimolecular fluorescence complementation experiments revealed the dimerization ability of both the full length and the terminal-free (CORE) TPPP/p25 forms, however, while TPPP/p25 aligned along the bundled microtubule network, the associated CORE segments distributed mostly homogeneously within the cytosol. Now, we identified a molecular model from the possible ones suggested in the Skoufias’s paper that could be responsible for stabilization of the microtubule network in the course of the oligodendrocyte differentiation, consequently in the constitution of the myelin sheath.

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Section: Discussionmentioning

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Further evidence for microtubule-independent dimerization of TPPP/p25

Oláh

Szénási

Szunyogh

et al. 2017

Sci Rep

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Interactions between two regulatory proteins of microtubule dynamics, HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8

Oláh¹,

Szunyogh²,

Szénási³

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Degradation of unwanted proteins is important in protein quality control cooperating with the dynein/dynactin-mediated trafficking along the acetylated microtubule (MT) network. Proteins associated directly/indirectly with tubulin/MTs play crucial roles in both physiological and pathological processes. Our studies focus on the interrelationship of the tubulin deacetylase HDAC6, the MT-associated TPPP/p25 with its deacetylase inhibitory potency and the hub dynein light chain DYNLL/LC8, constituent of dynein and numerous other protein complexes. In this paper, evidence is provided for the direct interaction of DYNLL/LC8 with TPPP/p25 and HDAC6 and their assembly into binary/ternary complexes with functional potency. The in vitro binding data was obtained with recombinant proteins and used for mathematical modelling. These data and *REVISED Manuscript (text UNmarked) Click here to view linked References

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Localization of the zinc binding tubulin polymerization promoting protein in the mice and human eye

Tripon

Oláh

Nasir

et al. 2018

Journal of Trace Elements in Medicine and Biology

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Tubulin Polymerization Promoting Protein (TPPP/p25) modulates the dynamics and stability of the microtubule network by its bundling and acetylation enhancing activities that can be modulated by the binding of zinc to TPPP/p25. Its expression is essential for the differentiation of oligodendrocytes, the major constituents of the myelin sheath, and has been associated with neuronal inclusions. In this paper, evidence is provided for the expression and localization of TPPP/p25 in the zinc-rich retina and in the oligodendrocytes in the optic nerve. Localization of TPPP/p25 was established by confocal microscopy using calbindin and synaptophysin as markers of specific striations in the inner plexiform layer (IPL) and presynaptic terminals, respectively. Postsynaptic nerve terminals in striations S1, S3 and S5 in the IPL and a subset of amacrine cells show immunopositivity against TPPP/p25 both in mice and human eyes. The co-localization of TPPP/p25 with acetylated tubulin was detected in amacrine cells, oligodendrocyte cell bodies and in synapses in the IPL. Quantitative Western blot revealed that the TPPP/p25 level in the retina was 0.05-0.13 ng/μg protein, comparable to that in the brain. There was a central (from optic nerve head) to peripheral retinal gradient in TPPP/p25 protein levels. Our in vivo studies revealed that the oral zinc supplementation of mice significantly increased TPPP/p25 as well as acetylated tubulin levels in the IPL. These results suggest that TPPP/p25, a microtubule stabilizer can play a role in the organization and reorganization of synaptic connections and visual integration in the eye.

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Zinc-induced structural changes of the disordered tppp/p25 inhibits its degradation by the proteasome

Cited by 10 publications

References 51 publications

Further evidence for microtubule-independent dimerization of TPPP/p25

Further evidence for microtubule-independent dimerization of TPPP/p25

Interactions between two regulatory proteins of microtubule dynamics, HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8

Localization of the zinc binding tubulin polymerization promoting protein in the mice and human eye

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