Spatial arrangement, polarity, and posttranslational modifications of the microtubule system in the Drosophila eye DOI Creative Commons

P. KOS,

Otto Baumann

Cell and Tissue Research, Journal Year: 2024, Volume and Issue: 398(2), P. 123 - 137

Published: Aug. 17, 2024

We have analyzed the organization of microtubule system in photoreceptor cells and pigment within adult Drosophila compound eye. Immunofluorescence localization tubulin Short stop, a spectraplakin that has been reported to be involved anchorage minus ends at membrane, suggests presence non-centrosomal microtubule-organizing centers distal tip visual cells. Ultrastructural analyses confirm microtubules emanate from membrane-associated plaques site contact with cone all are aligned distal-proximal direction Determination polarities demonstrated about 95% oriented their plus end synapse. Pigment eye contain only direction, pointing towards retinal floor. There, two populations can distinguished, single bundled microtubules, latter associated actin filaments. Whereas both acetylated mono/bi-glutamylated on α-tubulin, apparently also β-tubulin, providing possibility binding different microtubule-associated proteins.

Language: Английский

Tubulin detyrosination shapes Leishmania cytoskeletal architecture and virulence DOI Creative Commons
Rosa M. Corrales, Jeremy Vincent,

Lucien Crobu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(3)

Published: Jan. 14, 2025

Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While most organisms this modification restricted to α-tubulin, trypanosomatid parasites, it occurs on both α- β-tubulin. Here, we show that Leishmania , a single vasohibin (LmVASH) enzyme responsible differential kinetics of β-tubulin detyrosination. LmVASH knockout which are completely devoid detyrosination, decreased levels glutamylation exhibit strongly diminished pathogenicity mice, correlating with proliferation macrophages. Reduced virulence associated altered morphogenesis flagellum remodeling detyrosination-deficient amastigotes. Flagellum shortening the absence caused by hyperactivity microtubule-depolymerizing Kinesin-13 homolog, demonstrating its function as key reader trypanosomatid-tubulin code. Taken together, our work establishes importance tubulin microtubule-based cytoskeleton required efficient mammalian host. This highlights potential target therapeutic action against leishmaniasis.

Language: Английский

Citations

0
Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease DOI
Jia Jie Teoh, Francesca Bartolini

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 90, P. 102971 - 102971

Published: Jan. 24, 2025

Language: Английский

Citations

0
Tubulin posttranslational modifications through the lens of new technologies DOI Creative Commons
Gonzalo Alvarez Viar, Gaia Pigino

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102362 - 102362

Published: May 2, 2024

The Tubulin Code revolutionizes our understanding of microtubule dynamics and functions, proposing a nuanced system governed by tubulin isotypes, posttranslational modifications (PTMs) microtubule-associated proteins (MAPs). diverse across species, contribute structural complexity, are thought to influence functions. PTMs encode dynamic information on microtubules, which read several interacting impact cellular processes. Here we discuss recent technological methodological advances, such as in genome engineering, live cell imaging, expansion microscopy, cryo-electron microscopy that reveal new elements levels complexity the code, including modifying enzymes nanopatterns individual microtubules. Code's exploration holds transformative potential, guiding therapeutic strategies illuminating connections diseases like cancer neurodegenerative disorders, underscoring its relevance decoding fundamental language.

Language: Английский

Citations

2
Decoding microtubule detyrosination: enzyme families, structures, and functional implications DOI Creative Commons
Jitske Bak, Thijn R. Brummelkamp, Anastassis Perrakis

et al.

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(12), P. 1453 - 1464

Published: May 29, 2024

Microtubules are a major component of the cytoskeleton and can accumulate plethora modifications. The microtubule detyrosination cycle is one these modifications; it involves enzymatic removal C‐terminal tyrosine α‐tubulin on assembled microtubules re‐ligation detyrosinated tubulin dimers. This modification has been implicated in cardiac disease, neuronal development, mitotic defects. vasohibin microtubule‐associated carboxypeptidase enzyme families responsible for detyrosination. Their long‐sought discovery allows to review summarise differences similarities between two enzymes discuss how they interplay with other modifications functions code.

Language: Английский

Citations

1
Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation DOI
Kai He, Xiaobo Sun, Chuan Chen

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(2)

Published: Dec. 5, 2024

Tubulin polyglutamylation is a posttranslational modification that occurs primarily along the axoneme of cilia. Defective impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, precise mechanisms regulating proper remain vague. Here, we show cyclin-dependent kinase 6 (CDK6), but not its paralog CDK4, localizes to base suppresses by phosphorylating RAB11 family interacting protein 5 (FIP5) at site S641, critical regulator import glutamylases. S641 phosphorylation disrupts ciliary recruitment FIP5 association RAB11, thereby reducing Encouragingly, FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore in JBTS cells defective glutamylation. In summary, our study elucidates regulatory governing suggests developing CDK6-specific inhibitors could be promising therapeutic strategy enhance ciliopathy patients.

Language: Английский

Citations

1
Tubulin glycylation controls ciliary motility through modulation of outer-arm dyneins DOI
Tomohiro Kubo,

Rinka Sasaki,

Toshiyuki Oda

et al.

Molecular Biology of the Cell, Journal Year: 2024, Volume and Issue: 35(7)

Published: May 17, 2024

Tubulins undergo several kinds of posttranslational modifications (PTMs) including glutamylation and glycylation. The contribution these PTMs to the motilities cilia flagella is still unclear. Here, we investigated role tubulin glycylation by examining a novel Chlamydomonas mutant lacking TTLL3, an enzyme responsible for initiating Immunostaining cells revealed that only restricted axonemal composing outer-doublet but not central-pair microtubules. Furthermore, flagellar localization TTLL3 was found be dependent on intraflagellar transport. mutant, ttll3(ex5), completely lacks consequently exhibits slower swimming velocity compared with wild-type strain. By combining ttll3(ex5) mutation multiple dynein-deficient mutants, lack does affect motility outer-arm dynein mutations. Sliding disintegration assay using isolated axonemes decreases microtubule sliding in normal axoneme outerarm dyneins. Based our recent study occurs exclusively β-tubulin Chlamydomonas, findings suggest controls through modulating dyneins, presumably neutralizing negative charges glutamate residues at C-terminus region β-tubulin.

Language: Английский

Citations

0
Structural Characteristics and DNA Groove Binding Abilities of Two Zinc Based Isoreticular MOFs DOI

Taposi Chatterjee,

P.M. Guha, Basudeb Dutta

et al.

Chemistry - An Asian Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract In this study, we have synthesized two zinc(II)‐based metal‐organic frameworks (MOFs) designated as [Zn(4‐nvp)(bdc)] ⋅ (MeOH) ( 1 ) and [Zn 2 (4‐nvp) (bpdc) ] (DMF) [4‐nvp=4‐(1‐naphthylvinyl) pyridine, H bdc=1,4‐benzendicarboxylic acid bpdc=4,4′‐biphenyldicarboxylic acid]. Single‐crystal X‐ray diffraction (SCXRD) of both compounds unveiled an interesting paddle‐wheel (O C−C) 4 secondary building block (SBB) composed dinuclear Zn (II) centers four dicarboxylate groups with a (4,4) square grid topology. These SBBs are interconnected giving rise to infinite 2D layer architecture. Notably, the structure is MeOH molecules in compound DMF , them arranged free lattice. compounds, 3D supramolecular architecture ultimately formed through stacking layers. Since length bpdc ligand higher than that bdc ligand, solvent‐accessible void volume comparatively for . To corroborate all non‐bonded interactions, Hirshfeld analysis was carried out compounds. DNA binding application extensively investigated docking study. Results indicated strong affinities towards via groove binding. Henceforth, would open door their potential applications particular protein binders bioactive substances.

Language: Английский

Citations

0
Systematic Identification of Microtubule Posttranslational Modification “Readers” by Quantitative Proteomics DOI
Takashi Hotta, Ryoma Ohi

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 189 - 203

Published: Dec. 1, 2024

Language: Английский

Citations

0
Consciousness and the Axon Initial Segment DOI
Majid Beshkar

Integrative Psychological and Behavioral Science, Journal Year: 2024, Volume and Issue: 59(1)

Published: Dec. 19, 2024

Language: Английский

Citations

0
Spatial arrangement, polarity, and posttranslational modifications of the microtubule system in the Drosophila eye DOI Creative Commons

P. KOS,

Otto Baumann

Cell and Tissue Research, Journal Year: 2024, Volume and Issue: 398(2), P. 123 - 137

Published: Aug. 17, 2024

We have analyzed the organization of microtubule system in photoreceptor cells and pigment within adult Drosophila compound eye. Immunofluorescence localization tubulin Short stop, a spectraplakin that has been reported to be involved anchorage minus ends at membrane, suggests presence non-centrosomal microtubule-organizing centers distal tip visual cells. Ultrastructural analyses confirm microtubules emanate from membrane-associated plaques site contact with cone all are aligned distal-proximal direction Determination polarities demonstrated about 95% oriented their plus end synapse. Pigment eye contain only direction, pointing towards retinal floor. There, two populations can distinguished, single bundled microtubules, latter associated actin filaments. Whereas both acetylated mono/bi-glutamylated on α-tubulin, apparently also β-tubulin, providing possibility binding different microtubule-associated proteins.

Language: Английский

Citations

0