The Emerging Roles of Axonemal Glutamylation in Regulation of Cilia Architecture and Functions

Yang, Wen‐Ting; Hong, Shi; He, Kai; Ling, Kun; Shaiv, Kritika; Hu, Jing; Lin, Yu

doi:10.3389/fcell.2021.622302

Cited by 20 publications

(20 citation statements)

References 169 publications

(336 reference statements)

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“…The retrograde motor IFT-dynein is carried on anterograde trains by IFT-B (Pedersen et al, 2006;Jordan et al, 2018), via IFT54 (TRAF3IP1) (Zhu et al, 2020) and IFT172 (Williamson et al, 2012). IFT70 (TTC30A and TTC30B, also known as Fleer in zebrafish and DYF-1 in C. elegans) was proposed to be an adaptor for tubulin polyglutamylation enzymes (Pathak et al, 2007;Yang et al, 2021). Tubulin, the most abundant ciliary protein, can enter cilia by both diffusion and IFT, but requires IFT to support rapid ciliary growth (Craft et al, 2015;Craft Van De Weghe et al, 2020).…”

Section: Transporting Cargoes By Iftmentioning

confidence: 99%

The structural basis of intraflagellar transport at a glance

Jordan

Pigino

2021

Journal of Cell Science

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The intraflagellar transport (IFT) system is a remarkable molecular machine used by cells to assemble and maintain the cilium, a long organelle extending from eukaryotic cells that gives rise to motility, sensing and signaling. IFT plays a critical role in building the cilium by shuttling structural components and signaling receptors between the ciliary base and tip. To provide effective transport, IFT-A and IFT-B adaptor protein complexes assemble into highly repetitive polymers, called IFT trains, that are powered by the motors kinesin-2 and IFT-dynein to move bidirectionally along the microtubules. This dynamic system must be precisely regulated to shuttle different cargo proteins between the ciliary tip and base. In this Cell Science at a Glance article and the accompanying poster, we discuss the current structural and mechanistic understanding of IFT trains and how they function as macromolecular machines to assemble the structure of the cilium.

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Section: Transporting Cargoes By Iftmentioning

confidence: 99%

The structural basis of intraflagellar transport at a glance

Jordan

Pigino

2021

Journal of Cell Science

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“…Many microtubule‐based structures including primary cilia, centrosomes, mitotic spindles, and intercellular bridges regulate various cellular activities in a defined spatiotemporal manner (Doxsey et al , 2005 ; Prosser & Pelletier, 2017 ; Antanavičiūtė et al , 2018 ; Yang et al , 2021 ). We next tested whether the recruitment of dNSpastin3Q onto these different microtubule‐based structures can specifically disassemble them.…”

Section: Resultsmentioning

confidence: 99%

“…Different microtubule subpopulations undergo distinct post‐translational modifications (PTMs), which modulate their properties and functions (Janke & Magiera, 2020 ). Moreover, cells form several microtubule‐based structures spatiotemporally such as primary cilia on the surface of G0 cells, intercellular bridges in the connected regions of two dividing cells during telophase, mitotic spindles in the cytosol of metaphase cells, and centrosomes in the perinuclear region or cell cortex to execute corresponding activities (Doxsey et al , 2005 ; Prosser & Pelletier, 2017 ; Antanavičiūtė et al , 2018 ; Yang et al , 2021 ). Defects in these microtubules and relative structures lead to a variety of human diseases including birth defects, neurodegenerative diseases, ciliopathies, and several tumors, highlighting their essential roles (Hildebrandt et al , 2011 ; Parker et al , 2014 ; Sferra et al , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Precise control of microtubule disassembly in living cells

et al. 2022

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Microtubules tightly regulate various cellular activities. Our understanding of microtubules is largely based on experiments using microtubule-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific microtubule populations, due to their slow effects on the entire pool of microtubules. To overcome this technological limitation, we have used chemo and optogenetics to disassemble specific microtubule subtypes, including tyrosinated microtubules, primary cilia, mitotic spindles, and intercellular bridges, by rapidly recruiting engineered microtubule-cleaving enzymes onto target microtubules in a reversible manner. Using this approach, we show that acute microtubule disassembly swiftly halts vesicular trafficking and lysosomal dynamics. It also immediately triggers Golgi and ER reorganization and slows the fusion/fission of mitochondria without affecting mitochondrial membrane potential. In addition, cell rigidity is increased after microtubule disruption owing to increased contractile stress fibers. Microtubule disruption furthermore prevents cell division, but does not cause cell death during interphase. Overall, the reported tools facilitate detailed analysis of how microtubules precisely regulate cellular architecture and functions.

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“…In addition to cytosol MTs, many MT-based structures including primary cilia, centrosomes, mitotic spindles, and intercellular bridges regulate various cellular activities in a defined spatiotemporal manner [3][4][5][6] . We next tested whether recruitment of dNSpastinXXX onto these different MT-based structures can specifically disassemble them.…”

Section: Rapid Disruption Of Specific Mt-based Structuresmentioning

confidence: 99%

“…They are involved in many cellular activities including intracellular trafficking, cell migration, cell division, cell polarity, signaling, and others 1,2 . To execute these functions, cells form several MT-based structures spatiotemporally such as primary cilia on the surface of G0 cells, intercellular bridges in the connected regions of two dividing cells during telophase, mitotic spindles in the cytosol of metaphase cells, and centrosomes [3][4][5][6] . Our understanding of MTs and these MT-based organelles is largely dependent on MT-targeting agents (MTAs) that perturb MT dynamics 7 .…”

Section: Introductionmentioning

confidence: 99%

Precise control of microtubule disassembly in living cells

Liu

Chen

Shaiv

et al. 2021

Preprint

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Microtubules (MTs) are components of the evolutionarily conserved cytoskeleton, which tightly regulates various cellular activities. Our understanding of MTs is largely based on MT-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific MT populations due to their slow effects on the entire pool of MTs in cells. To address this limitation, we have used chemogenetics and optogenetics to disassemble specific MT subtypes by rapid recruitment of engineered MT-cleaving enzymes. Acute MT disassembly swiftly halted vesicular trafficking and lysosome dynamics. We also used this approach to disassemble MTs specifically modified by tyrosination and several MT-based structures including primary cilia, mitotic spindles, and intercellular bridges. These effects were rapidly reversed by inhibiting the activity or MT association of the cleaving enzymes. The disassembly of targeted MTs with spatial and temporal accuracy enables to uncover new insights of how MTs precisely regulate cellular architectures and functions.

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The Emerging Roles of Axonemal Glutamylation in Regulation of Cilia Architecture and Functions

Cited by 20 publications

References 169 publications

The structural basis of intraflagellar transport at a glance

The structural basis of intraflagellar transport at a glance

Precise control of microtubule disassembly in living cells

Precise control of microtubule disassembly in living cells

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