Manipulating Cellular Activities Using an Ultrasound–Chemical Hybrid Tool

Fan, Chih‐Peng; Huang, Yao Shen; Huang, Wei E.; Lee, Albert Alexander; Ho, Sheng Yang; Kao, Yu Lin; Wang, Cuei Ling; Lian, Yen Ling; Ueno, Takahiro; Wang, Tsung-Shing Andrew; Yeh, Chih Kuang; Lin, Yu

doi:10.1021/acssynbio.7b00162

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…The approaches developed here have powerful applications beyond probing diffusion mechanisms. Chemically inducible dimerization systems have been widely used to spatiotemporally manipulate cellular architecture and signaling by recruiting proteins of interest (Rs of ≤ 5.1 nm) onto target sites in cells (18,(59)(60)(61). The current study has established a new system that enables rapid recruitment of proteins of interest onto the centrioles, pericentriolar matrix, or centriolar satellites within seconds.…”

Section: Discussionmentioning

confidence: 99%

Actin filaments act as a size-dependent diffusion barrier around centrosomes

Cheng

Kao

Sharma

et al. 2021

Preprint

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The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that the centrosome may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we found that centrosomes were highly accessible to soluble molecules with a Stokes radius of ≤ 5.1 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of barriers was tightly regulated by branched actin filaments outside of centrosomes. Such barrier gated the microtubule nucleation. We propose that actin filaments spatiotemporally constrain the distribution of molecules at centrosomes in a size-dependent manner.Significance StatementCentrosome maintains its microenvironment without membrane. Whether the dense protein complexes outside centrosomes including pericentriolar matrix, microtubules, and branched actin filaments provide physical obstruction is unclear yet. We here established a series of new tools for quantitative evaluation of the diffusion rates of varisized soluble proteins in different sub-compartments of centrosomes. Our results demonstrated that branched actin filaments, but not pericentriolar matrix or microtubules, around centrosome have acted as a size-dependent diffusion barrier and physically constrain centrosome microtubule nucleation.

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Section: Discussionmentioning

confidence: 99%

Actin filaments act as a size-dependent diffusion barrier around centrosomes

Cheng

Kao

Sharma

et al. 2021

Preprint

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“…The addition of rapamycin brings the FKBP fusion protein to the FRB-residual site where the FKBP-tagged protein of interest can access its substrates or downstream signaling molecules to locally manipulate the corresponding molecular activities. Thus far, the IPD system has been extensively used to manipulate the activity of small GTPases, lipid homeostasis, cellular mechanotransduction, and so on (Varnai et al, 2006;Zoncu et al, 2007;Bohdanowicz and Fairn, 2011;DeRose et al, 2012;Fan et al, 2017;Wang Y. et al, 2019).…”

Section: New Methods Enabling the Spatiotemporal Manipulation Of Axonmentioning

confidence: 99%

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

Yang

Hong

et al. 2021

Front. Cell Dev. Biol.

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Cilia, which either generate coordinated motion or sense environmental cues and transmit corresponding signals to the cell body, are highly conserved hair-like structures that protrude from the cell surface among diverse species. Disruption of ciliary functions leads to numerous human disorders, collectively referred to as ciliopathies. Cilia are mechanically supported by axonemes, which are composed of microtubule doublets. It has been recognized for several decades that tubulins in axonemes undergo glutamylation, a post-translational polymodification, that conjugates glutamic acid chains onto the C-terminal tail of tubulins. However, the physiological roles of axonemal glutamylation were not uncovered until recently. This review will focus on how cells modulate glutamylation on ciliary axonemes and how axonemal glutamylation regulates cilia architecture and functions, as well as its physiological importance in human health. We will also discuss the conventional and emerging new strategies used to manipulate glutamylation in cilia.

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“…The chemically inducible dimerization (CID) system has been used to manipulate cellular signaling and molecular composition over both space and time [12][13][14] . This is achieved by the rapid recruitment of proteins of interest (POIs) onto specific subcellular sites or their substrates 12 .…”

Section: Rapid Translocation Of Proteins Of Interest Onto Mtsmentioning

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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Manipulating Cellular Activities Using an Ultrasound–Chemical Hybrid Tool

Cited by 11 publications

References 27 publications

Actin filaments act as a size-dependent diffusion barrier around centrosomes

Actin filaments act as a size-dependent diffusion barrier around centrosomes

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

Precise control of microtubule disassembly in living cells

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