A Brain‐Specific Protein p25 Is Localized and Associated with Oligodendrocytes, Neuropil, and Fiber‐Like Structures of the CA3 Hippocampal Region in the Rat Brain

Takahashi, Miho; Tomizawa, Kayoko; Fujita, Shinobu C.; Sato, Kazuki; Uchida, Tsuneko; Imahori, Kazutomo

doi:10.1111/j.1471-4159.1993.tb05842.x

Cited by 74 publications

(80 citation statements)

References 21 publications

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“…9). The specificity is further supported by the unique fact that the assembly of these two disordered hallmarks occurs exclusively at pathological conditions since in normal brain SYN and TPPP/p25 are expressed in neurons [57,58] and oligodendrocytes [9,59], respectively. Previously we showed that TPPP/p25, similarly to SYN, could be taken up by cells from the medium [35].…”

Section: Discussionmentioning

confidence: 82%

Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

Szénási¹,

Oláh²,

Szabó³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The hallmarks of Parkinson's disease and other synucleinopathies, Tubulin Polymerization Promoting Protein (TPPP/p25) and α-synuclein (SYN) have two key features: they are disordered and co-enriched/co-localized in brain inclusions. These Neomorphic Moonlighting Proteins display both physiological and pathological functions due to their interactions with distinct partners. To achieve the selective targeting of the pathological TPPP/p25-SYN but not the physiological TPPP/ p25-tubulin complex, their interfaces were identified as a specific innovative strategy for the development of anti-Parkinson drugs. Therefore, the interactions of TPPP/p25 with tubulin and SYN were characterized which suggested the involvements of the 178-187 aa and 147-156 aa segments in the complexation of TPPP/p25 with tubulin and SYN, respectively. However, various truncated and deletion mutants reduced but did not abolish the interactions except one mutant; in addition synthetized fragments corresponding to the potential binding segments of TPPP/p25 failed to interact with SYN. In fact, the studies of the multiple interactions at molecular and cellular levels revealed the high conformational plasticity, chameleon feature, of TPPP/p25 that ensures exceptional functional resilience; the lack of previously identified binding segments could be replaced by other segments. The experimental results are underlined by distinct bioinformatics tools. All these data revealed that although targeting chameleon proteins is a challenging task, nevertheless, the validation of a drug target can be achieved by identifying the interface of complexes of the partner proteins existing at the given pathological conditions.

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Section: Discussionmentioning

confidence: 82%

Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

Szénási¹,

Oláh²,

Szabó³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…It is known that both TPPP1 and TPPP3 can be found in adult brains of various mammals. The exact localization of TPPP3 in brain is not known but TPPP1 can be found physiologically in oligodendroglia not in neurons [21][22][23]. Whilst TPPP1 seems to be brain-specific, TPPP3 has been found in other tissues as well [24][25][26].…”

Section: Tppps Of the Zebrafish (Danio Rerio)mentioning

confidence: 99%

“…The developmental expression of TPPP1 in rat brain shows that it is practically absent in embryos and after birth its amount increases continuously by aging [21]. On the contrary, mammalian TPPP2 is absent in adult brain but is expressed in fetal one [27]; i.e.…”

Section: Tppps Of the Zebrafish (Danio Rerio)mentioning

confidence: 99%

On the tubulin polymerization promoting proteins of zebrafish

Orosz

2015

Biochemical and Biophysical Research Communications

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.] in which they identified possible downstream genes required for the extension of peripheral axons in primary sensory neurons of zebrafish. Tppp was claimed as one of the several candidate genes. However, there is confusion in the paper since the three tppp paralogs are mixed up. In the text tppp is mentioned and the properties of vertebrate TPPP1(tubulin polymerization-promoting protein) are discussed. It is claimed that its expression was investigated in various tissues. However, the supplementary table showing the genes investigated lists not tppp but "tubulin polymerization-promoting protein family member 3" i.e. tppp3. To reach a complete confusion, the NCBI Accession number XM_682834 is given in a table, which is the mRNA of the tubulin polymerization-promoting protein family member 3-like gene according to the NCBI Database.Thus it seems to be necessary to clarify this question.As I show in the submitted paper, it is the tppp3-like gene, a paralog of tppp, which plays this role. This finding raises further the significance of Aoki and his co-workers' paper since it is the very first one which provides experimental data about a tppp3-like gene.In the other part of the paper, I clarify the position of the tppp3-like genes, found exclusively in fishes, in the family of TPPP-like proteins showing that they are the orthologs of human TPPP2.I hope that the paper is suitable for publication in your journal. tppp1 (named also tppp), tppp3 and tppp3-like. Tppp1 and tppp3 are the orthologs of the corresponding human genes, however, the classification of the third one is ambiguous. It is known that the genomes of the early vertebrate lineage underwent two complete genome duplications, which result in the presence of several paralogs in vertebrates. A teleost fish specific third whole genome duplication also occurred. Thus the tppp3-like gene can be either an ortholog of human TPPP2 or a fourth paralog (tppp4) absent in tetrapods but present in fishes; finally a tppp3a gene which can be originated from the third, fish specific, whole genome duplication. Comparing the sequences of vertebrate and recently available lamprey tppps I show that the tppp3-like gene is a TPPP2 ortholog.Synteny data are in accordance with this suggestion.

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“…However, the protein has been found only in rats and bovines (8). Immunohistochemical studies showed TPPP/p25 in oligodendrocytes of human brain tissue and to be increased by age (22). By a novel affinity technique, TPPP/p25 was found in association with rat complexin, one of the ten structural proteins probably involved in synaptic structural reorganization (23).…”

mentioning

confidence: 99%

What is the biological significance of the brain-specific tubulin-polymerization promoting protein (TPPP/p25)?

Ovádi

Orosz

Lebotzky

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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A Brain‐Specific Protein p25 Is Localized and Associated with Oligodendrocytes, Neuropil, and Fiber‐Like Structures of the CA3 Hippocampal Region in the Rat Brain

Cited by 74 publications

References 21 publications

Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

Challenging drug target for Parkinson's disease: Pathological complex of the chameleon TPPP/p25 and alpha-synuclein proteins

On the tubulin polymerization promoting proteins of zebrafish

What is the biological significance of the brain-specific tubulin-polymerization promoting protein (TPPP/p25)?

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