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

Tripon, Robert Gabriel; Oláh, Judit; Nasir, Tajwar; Csincsik, Lajos; Li, Chee Lok; Szunyogh, Sándor; Gong, Haiyan; Flinn, Jane M.; Ovádi, Judit; Lengyel, Imre

doi:10.1016/j.jtemb.2017.12.009

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…TPPP/p25 localization in nerve terminals of mice and human retina has been identified; OLGs in the myelin ensheathment of optic nerve, postsynaptic nerve terminals in striations of the inner plexiform layer and a subset of amacrine cells showed immunopositivity for TPPP/p25 both in mice and human eyes [36]. The co-localization of TPPP/p25 with acetylated tubulin was detected in amacrine cells, OLG cell bodies and in synapses in the inner plexiform layer that is rich in neuropil, in which the occurrence of TPPP/p25 has been detected.…”

Section: Tppp Homologs Are Extensively Wide-spreadmentioning

confidence: 97%

Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night

Oláh

Lehotzky

Szunyogh

et al. 2020

Cells

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The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeleton, including the microtubule network. Microtubules play crucial roles achieved by their decoration with proteins/enzymes as well as by posttranslational modifications. This review focuses on the Tubulin Polymerization Promoting Protein (TPPP/p25), a new microtubule associated protein, on its “regulatory functions by day and pathological functions at night”. Physiologically, the moonlighting TPPP/p25 modulates the dynamics and stability of the microtubule network by bundling microtubules and enhancing the tubulin acetylation due to the inhibition of tubulin deacetylases. The optimal endogenous TPPP/p25 level is crucial for its physiological functions, to the differentiation of oligodendrocytes, which are the major constituents of the myelin sheath. Pathologically, TPPP/p25 forms toxic oligomers/aggregates with α-synuclein in neurons and oligodendrocytes in Parkinson’s disease and Multiple System Atrophy, respectively; and their complex is a potential therapeutic drug target. TPPP/p25-derived microtubule hyperacetylation counteracts uncontrolled cell division. All these issues reveal the anti-mitotic and α-synuclein aggregation-promoting potency of TPPP/p25, consistent with the finding that Parkinson’s disease patients have reduced risk for certain cancers.

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Section: Tppp Homologs Are Extensively Wide-spreadmentioning

confidence: 97%

Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night

Oláh

Lehotzky

Szunyogh

et al. 2020

Cells

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“…Similar to Ringer, TPPP in zebrafish has been implicated in axon outgrowth (Aoki et al, 2014; Orosz, 2015). While a recent report described TPPP localization in nerve terminals of mice and human retina (Tripon et al, 2018), the role of Ringer or any TPPP family of proteins in other species in regulating MT organization during synaptic development and function remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Tubulin Polymerization Promoting Protein, Ringmaker, and MAP1B Homolog Futsch Coordinate Microtubule Organization and Synaptic Growth

Shi

Lin

Saliba

et al. 2019

Front. Cell. Neurosci.

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Drosophila Ringmaker (Ringer) is homologous to the human T ubulin P olymerization P romoting P roteins (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 M icrotubule A ssociated P rotein (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.

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“…Elevated IOP seems to decrease the MAP1A amount and, thereby, the number of axonal cross-bridges, leading to microtubule instability and abnormal organelle transportation in axon plasma [ 72 ]. TPPPs show extensive MT bundling and polymerization abilities critical for axon formation, extension, and guidance at nerve terminals, as demonstrated in retinae of the model organisms drosophila, zebrafish, mouse, and human [ 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. A study investigating AD showed TPPP down-regulation [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamin-like Protein 1 (DNML1) as a Molecular Target for Antibody-Based Immunotherapy to Treat Glaucoma

Tonner¹,

Hunn²,

Auler³

et al. 2022

IJMS

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Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma, the second leading cause of blindness worldwide. Previous studies have shown that impaired mitochondrial dynamics could facilitate retinal neurodegeneration. Mitochondrial dynamics are regulated directly (fission) or more indirectly (fusion) by dynamin-like protein 1 (DNML1). Therefore, DNM1L might be a promising target for an antibody-based approach to treat glaucoma. The consequences of targeting endogenous DNM1L by antibodies in a glaucoma animal model have not been investigated yet. Here, we show that the intravitreal application of an anti-DNM1L antibody showed protective effects regarding the survival of RGCs and their axons in the retinal nerve fiber layer (RNFL). Antibody treatment also improved retinal functionality, as observed by electroretinography (Ganzfeld ERG). Western blot analysis revealed altered DNM1L phosphorylation and altered expression of proteins related to apoptosis suggesting a decreased apoptosis rate. Mass spectrometry analysis revealed 28 up-regulated and 21 down-regulated proteins (p < 0.05) in both experimental groups. Protein pathway analysis showed that many proteins interacted directly with the target protein DNM1L and could be classified into three main protein clusters: Vesicle traffic-associated (NSF, SNCA, ARF1), mitochondrion-associated (HSP9A, SLC25A5/ANT2, GLUD1) and cytoskeleton-associated (MAP1A) signaling pathway. Our results demonstrate that DNM1L is a promising target for an antibody-based approach to glaucoma therapy.

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

Cited by 3 publications

References 47 publications

Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night

Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night

Tubulin Polymerization Promoting Protein, Ringmaker, and MAP1B Homolog Futsch Coordinate Microtubule Organization and Synaptic Growth

Dynamin-like Protein 1 (DNML1) as a Molecular Target for Antibody-Based Immunotherapy to Treat Glaucoma

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