Reviewer #1 (Public Review): The TTLL10 polyglycylase is stimulated by tubulin glutamylation and inhibited by polyglycylation DOI Open Access

Опубликована: Июль 12, 2024

Microtubules in cells have complex and developmentally stereotyped posttranslational modifications that support diverse processes such as cell division, ciliary growth axonal specification. Glycylation, the addition of glycines, singly (monoglycylation) or chains (polyglycylation), is primarily found on axonemal microtubules where it functions cilia maintenance motility. It catalyzed by three enzymes tubulin tyrosine ligase- like family, TTLL3, 8 10. We show TTLL8 monoglycylates both α- β-tubulin, unlike TTLL3 which prefers β-tubulin. Microscopy mass spectrometry TTLL10 requires monoglycylation for high affinity microtubule binding elongates polyglycine only from pre-existing glycine branches. Surprisingly, polyglycylation inhibits recruitment to proportional with number posttranslationally added suggesting an autonomous mechanism chain length control. In contrast, glutamylation, precedes cilia, increases microtubules, a sequential deposition axonemes. Our work sheds light how code written establishing substrate preference regulation TTLL glycylases, provides minimal system generating differentially glycylated vitro analyses code.

Язык: Английский

The Tubulin Code, from Molecules to Health and Disease DOI Creative Commons

Elizabeth D. McKenna,

Stephanie L. Sarbanes,

Steven W. Cummings

и другие.

Annual Review of Cell and Developmental Biology, Год журнала: 2023, Номер 39(1), С. 331 - 361

Опубликована: Окт. 16, 2023

Microtubules are essential dynamic polymers composed of α/β-tubulin heterodimers. They support intracellular trafficking, cell division, cellular motility, and other processes. In many species, both α-tubulin β-tubulin encoded by multiple genes with distinct expression profiles functionality. further diversified through abundant posttranslational modifications, which added removed a suite enzymes to form complex, stereotyped arrays. The genetic chemical diversity tubulin constitute code that regulates intrinsic microtubule properties is read effectors, such as molecular motors microtubule-associated proteins, provide spatial temporal specificity microtubules in cells. this review, we synthesize the rapidly expanding literature highlight limitations opportunities for field. As complex arrays underlie physiological processes, better understanding how cells employ has important implications human disease ranging from cancer neurological disorders.

Язык: Английский

Процитировано

47
Tubulin polyglutamylation differentially regulates microtubule‐interacting proteins DOI Creative Commons
Mariya Genova, Lenka Grycová,

Verena Puttrich

и другие.

The EMBO Journal, Год журнала: 2023, Номер 42(5)

Опубликована: Янв. 13, 2023

Язык: Английский

Процитировано

33
Microtubule-binding protein MAP1B regulates interstitial axon branching of cortical neurons via the tubulin tyrosination cycle DOI Creative Commons
Jakub Žiak,

Joelle M. Dorskind,

Brian Trigg

и другие.

The EMBO Journal, Год журнала: 2024, Номер 43(7), С. 1214 - 1243

Опубликована: Фев. 22, 2024

Abstract Regulation of directed axon guidance and branching during development is essential for the generation neuronal networks. However, molecular mechanisms that underlie interstitial (or collateral) in mammalian brain remain unresolved. Here, we investigate vivo using an approach precise labeling layer 2/3 callosal projection neurons (CPNs). This method allows quantitative analysis axonal morphology at high acuity also manipulation gene expression well-defined temporal windows. We find GSK3β serine/threonine kinase promotes CPNs by releasing MAP1B-mediated inhibition branching. Further, tubulin tyrosination cycle a key downstream component GSK3β/MAP1B signaling. These data suggest cell-autonomous regulation cortical neuron morphology, which can release brake on upstream posttranslational code.

Язык: Английский

Процитировано

10
Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons DOI Creative Commons
Ana Catarina Costa, Blanca R Murillo,

Rita Bessa

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Фев. 24, 2025

Sensory dorsal root ganglion (DRG) neurons have a unique pseudo-unipolar morphology in which stem axon bifurcates into peripheral and central axon, with different regenerative abilities. Whereas DRG axons regenerate, are unable to regrow. Central regeneration can however be elicited by prior conditioning lesion the axon. How asymmetry is established remains unknown. Here we developed rodent vitro system replicating pseudo-unipolarization asymmetric regeneration. Using this model, observed that from early development, higher density of growing microtubules. This was also present vivo abolished decreased microtubule polymerization axons. An axon-specific microtubule-associated protein (MAP) signature, including severases spastin katanin regulators CRMP5 tau, found shown adapt upon lesion. Supporting its significance, interfering MAP signature either or readily central-peripheral asymmetries dynamics ability. In summary, our data unveil regulation drives sensory neuron

Язык: Английский

Процитировано

1
Glutamylation is a negative regulator of microtubule growth DOI
Jiayi Chen, Antonina Roll‐Mecak

Molecular Biology of the Cell, Год журнала: 2023, Номер 34(7)

Опубликована: Апрель 19, 2023

Microtubules are noncovalent polymers built from αβ-tubulin dimers. The disordered C-terminal tubulin tails functionalized with multiple glutamate chains of variable lengths added and removed by tyrosine ligases (TTLLs) carboxypeptidases (CCPs). Glutamylation is abundant on stable microtubule arrays such as in axonemes axons, its dysregulation leads to human pathologies. Despite this, the effects glutamylation intrinsic dynamics unclear. Here we generate short long show that slows rate growth increases catastrophes a function levels. This implies higher stability glutamylated microtubules cells due effectors. Interestingly, EB1 minimally affected thus can report rates both unmodified microtubules. Finally, removal CCP1 5 synergistic occurs preferentially soluble tubulin, unlike TTLL enzymes prefer substrate preference establishes an asymmetry whereby once depolymerizes, released reset less-modified state, while polymerized accumulates mark. Our work shows modification directly affect furthers our understanding mechanistic underpinnings code.

Язык: Английский

Процитировано

12
TUBB3 and KIF21A in neurodevelopment and disease DOI Creative Commons
Dharmendra Puri, Brenda J. Barry, Elizabeth C. Engle

и другие.

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Авг. 4, 2023

Neuronal migration and axon growth guidance require precise control of microtubule dynamics microtubule-based cargo transport. TUBB3 encodes the neuronal-specific β-tubulin isotype III, TUBB3, a component neuronal microtubules expressed throughout life central peripheral neurons. Human pathogenic missense variants result in altered function cause errors either cranial and, to lesser extent, axons, or cortical organization, rarely both. Moreover, human KIF21A , which an anterograde kinesin motor protein that interacts directly with microtubules, alter can phenocopy variants. Here, we review reported variants, resulting phenotypes, corresponding functional studies both wildtype mutant proteins. We summarize evidence that, vitro mouse models, loss-of-function microtubule-kinesin interactions. Lastly, highlight additional might contribute our understanding relationship between specific tubulin isotypes proteins health disease.

Язык: Английский

Процитировано

12
Structural basis for α-tubulin-specific and modification state-dependent glutamylation DOI

Kishore K. Mahalingan,

Danielle A. Grotjahn, Yan Li

и другие.

Nature Chemical Biology, Год журнала: 2024, Номер 20(11), С. 1493 - 1504

Опубликована: Апрель 24, 2024

Язык: Английский

Процитировано

5
A family of carboxypeptidases catalyzing α- and β-tubulin tail processing and deglutamylation DOI Creative Commons
Simon Nicot, Ghislain Gillard, Hathaichanok Impheng

и другие.

Science Advances, Год журнала: 2023, Номер 9(37)

Опубликована: Сен. 13, 2023

Tubulin posttranslational modifications represent an important mechanism involved in the regulation of microtubule functions. The most widespread among them are detyrosination, α∆2-tubulin, and polyglutamylation. Here, we describe a family tubulin-modifying enzymes composed two closely related proteins, KIAA0895L KIAA0895, which have tubulin metallocarboxypeptidase activity thus were termed TMCP1 TMCP2, respectively. We show that (also known as MATCAP) acts α-tubulin detyrosinase also catalyzes α∆2-tubulin. In contrast, TMCP2 preferentially modifies βI-tubulin by removing three amino acids from its C terminus, generating previously unknown βI∆3 modification. βI∆3-tubulin is mostly found on centrioles mitotic spindles cilia. Moreover, demonstrate TMCPs remove polyglutamylation act deglutamylases. Together, our study describes identification comprehensive biochemical analysis type processing α- β-tubulin C-terminal tails deglutamylation.

Язык: Английский

Процитировано

10
Microtubule-binding domains in Katanin p80 subunit are essential for severing activity in C. elegans DOI Creative Commons
Eva Beaumale, Lucie Van Hove, Lionel Pintard

и другие.

The Journal of Cell Biology, Год журнала: 2024, Номер 223(4)

Опубликована: Фев. 8, 2024

Microtubule-severing enzymes (MSEs), such as Katanin, Spastin, and Fidgetin play essential roles in cell division neurogenesis. They damage the microtubule (MT) lattice, which can either destroy or amplify MT cytoskeleton, depending on cellular context. However, little is known about how they interact with their substrates. We have identified microtubule-binding domains (MTBD) required for Katanin function C. elegans. a heterohexamer of dimers containing catalytic subunit p60 regulatory p80, both are female meiotic spindle assembly. Here, we report that p80-like(MEI-2) dictates binding to MTs via two MTBDs composed basic patches. Substituting these patches reduces MTs, compromising its meiotic-spindle Structural alignments p80s from different species revealed evolutionarily conserved, even if specific amino acids involved vary. Our findings highlight critical importance (p80) providing complex.

Язык: Английский

Процитировано

3
Tubulin code eraser CCP5 binds branch glutamates by substrate deformation DOI
Jiayi Chen, Elena A. Zehr, James M. Gruschus

и другие.

Nature, Год журнала: 2024, Номер 631(8022), С. 905 - 912

Опубликована: Июль 17, 2024

Язык: Английский

Процитировано

3