The molecular architecture of the ciliary transition zones

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102361 - 102361

Published: April 21, 2024

Cilia and flagella are specialized eukaryotic organelles projecting from the surface of cells that play a central role in various physiological processes, including cell motility, sensory perception, signal transduction. At base these structures lies ciliary transition zone, pivotal region functions as gatekeeper communication hub for activities. Despite its crucial role, intricacies architecture remain poorly understood, especially given variations organization across different types species. In this review, we explore molecular with particular focus on recent findings obtained using cryotomography super-resolution imaging techniques.

Language: Английский

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The evolution of centriole degradation in mouse sperm

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Centrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles flagellum essential for embryo development in basal animals. Yet, sperm have evolved diverse forms, sometimes acting like transmission system, as cattle, becoming dispensable, house mice. How centriole to become dispensable some organisms is unclear. Here, we test hypothesis that this transition occurred through cascade of evolutionary changes proteins, structure, function was possibly driven by competition. We final steps associated change primary centriolar inner scaffold protein FAM161A rodents. This information provides first insight into molecular mechanisms adaptive evolution underlying major within internal mammalian neck.

Language: Английский

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CCDC15 localizes to the centriole inner scaffold and controls centriole length and integrity

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(12)

Published: Nov. 7, 2023

Centrioles are microtubule-based organelles responsible for forming centrosomes and cilia, which serve as microtubule-organizing, signaling, motility centers. Biogenesis maintenance of centrioles with proper number, size, architecture vital their functions during development physiology. While centriole number control has been well-studied, less is understood about stable structures conserved size cell division ciliary motility. Here, we identified CCDC15 a protein that colocalizes interacts the inner scaffold, crucial centriolar subcompartment integrity. Using ultrastructure expansion microscopy, found depletion affects length integrity, leading to defective cilium formation, maintenance, response Hedgehog signaling. Moreover, loss-of-function experiments showed CCDC15’s role in recruiting both scaffold POC1B distal SFI1/Centrin-2 complex centrioles. Our findings reveal players mechanisms architectural integrity insights into diseases linked defects.

Language: Английский

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An interaction network of inner centriole proteins organised by POC1A-POC1B heterodimer crosslinks ensures centriolar integrity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 14, 2024

Abstract Centriole integrity, vital for cilia formation and chromosome segregation, is crucial human health. The inner scaffold within the centriole lumen composed of proteins POC1B, POC5 FAM161A key to this integrity. Here, we provide an understanding function proteins. We demonstrate importance interaction network organised by POC1A-POC1B heterodimers lumen, where WD40 domain POC1B localises close wall, while POC5-interacting POC1A resides in lumen. POC1A-POC5 tetramerization are essential stability. microtubule binding MDM1 POC1A-POC1B, likely positioning tetramer near wall. Disruption or leads defects deletion both genes causes disintegration. These findings insights into organisation scaffold.

Language: Английский

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A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture

Published: Feb. 6, 2025

Centrioles have a unique, conserved architecture formed by three linked “triplet” microtubules arranged in nine-fold symmetry. The mechanisms which these triplet are not understood and likely involve the noncanonical tubulins delta-tubulin epsilon-tubulin. Previously, we found that human cells deficient or epsilon-tubulin form abnormal centrioles, characterized an absence of microtubules, lack central core protein POC5, futile cycle centriole formation disintegration (Wang et al., 2017). Here, show lacking either associated proteins TEDC1 TEDC2 same phenotypes. Using ultrastructure expansion microscopy, find mutant centrioles elongate to length as control G2-phase. These mutants fail recruit inner scaffold expanded proximal region. During mitosis, further before fragmenting disintegrating. All four physically interact capable forming subcomplex tubulins. results support AlphaFold Multimer model tetramer predicted heterodimer. localize centrosomes mutually dependent on each other for localization. Our demonstrate delta-tubulin, epsilon-tubulin, TEDC1, function together promote robust architecture. This work also lays groundwork future molecular studies this complex, providing basis determining underlie assembly interplay between structure.

Language: Английский

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Poc1 bridges basal body inner junctions to promote triplet microtubule integrity and connections

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(8)

Published: May 14, 2024

Basal bodies (BBs) are conserved eukaryotic structures that organize cilia. They comprised of nine, cylindrically arranged, triplet microtubules (TMTs) connected to each other by inter-TMT linkages which stabilize the structure. Poc1 is a protein important for BB structural integrity in face ciliary forces transmitted BBs. To understand how confers stability, we identified precise position Tetrahymena and effect loss on binds at TMT inner junctions, stabilizing TMTs directly. From this location, also stabilizes throughout BB, including cartwheel pinhead scaffold. The full localization scaffold Fam161A requires Poc1. As increased, reduced, indicative force-dependent molecular remodeling Thus, while not essential assembly, promotes interconnections establish an architecture competent resist forces.

Language: Английский

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A ternary complex of MIPs in the A-tubule of basal bodies and axonemes depends on RIB22 and the EF-hand domain of RIB72A in Tetrahymena cilia

Molecular Biology of the Cell, Journal Year: 2025, Volume and Issue: 36(4)

Published: Feb. 12, 2025

The lumens of the highly stable microtubules that make up core basal bodies, cilia, and flagella are coated with a network proteins known as MIPs, or microtubule inner proteins. MIPs hypothesized to enhance rigidity stability these microtubules, but how they assemble contribute cilia function is poorly understood. Here we describe ciliate specific MIP, RIB22, in Tetrahymena thermophila. RIB22 calmodulin-like protein found A-tubule doublet triplet bodies. Its localization dependent on conserved MIP RIB72. use cryogenic electron tomography (cryoET) examine its interacting partners axonemes forms ternary complex C-terminal EF-hand domain RIB72A another FAM166A. strains lacking showed impaired function. CryoET from demonstrated an interdependence three for stabilization within structure. Deletion resulted apparent loss multiple region. These findings emphasize intricacy importance understanding MIPs’ functions during cilium assembly regulation.

Language: Английский

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The structure of basal body inner junctions from Tetrahymena revealed by electron cryo-tomography

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Abstract The cilium is a microtubule-based eukaryotic organelle critical for many cellular functions. Its assembly initiates at basal body and continues as an axoneme that projects out of the cell to form functional cilium. This process tightly regulated. However, our knowledge molecular architecture mechanism limited. By applying cryo-electron tomography, we obtained structures inner junction in three regions from Tetrahymena : proximal, central core body, axoneme. We identified several protein components body. While few proteins are distributed throughout entire length organelle, restricted specific regions, forming intricate local interaction networks bolstering structural stability. examining POC1 knockout mutant, found triplet microtubule was destabilized, resulting defective structure. Surprisingly, axoneme-specific were “infiltrate” into mutant Our findings provide insight junctions, underscoring its precise spatial regulation.

Language: Английский

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A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 11, 2025

Centrioles have a unique, conserved architecture formed by three linked, ‘triplet’, microtubules arranged in ninefold symmetry. The mechanisms which these triplet are remain unclear but likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we found that human cells lacking or epsilon-tubulin form abnormal centrioles, characterized an absence of microtubules, lack central core protein POC5, futile cycle centriole formation disintegration (Wang et al., 2017). Here, show either TEDC1 TEDC2 similar abnormalities. Using ultrastructure expansion microscopy, observed mutant centrioles elongate to same length as control G2 phase fail recruit scaffold proteins. Remarkably, also expanded proximal region. During mitosis, further before fragmenting disintegrating. All four proteins physically interact can subcomplex tubulins, supporting AlphaFold Multimer model tetramer. localize centrosomes mutually dependent on each other for localization. Our results demonstrate delta-tubulin, epsilon-tubulin, TEDC1, function together promote robust architecture, laying foundation future studies underlying assembly their interactions with structure.

Language: Английский

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Time and power dependence of laser-induced photodamage on human sperm revealed by longitudinal rolling measurement using optical tweezers

Biomedical Optics Express, Journal Year: 2024, Volume and Issue: 15(6), P. 3563 - 3563

Published: April 25, 2024

Lasers are widely applied in assisted reproductive technologies, including sperm fixation, selection and intracytoplasmic injections, to reduce procedure time improve consistency reproducibility. However, quantitative studies on laser-induced photodamage of lacking. In this study, we demonstrated that, by using optical tweezers, the kinematic parameters freely swimming correlated with frequency as well percentage pausing duration longitudinal rolling same head trap. Furthermore, trapping individual cells 1064-nm quantitatively characterized time-dependence under different laser powers. Our study revealed power increase, optically trapped decreases an increasing duration, which characterizes effect cells. provides experimental basis for optimization application technology, may photodamage-induced biosafety risk future.

Language: Английский

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