Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier

Takanari Inoue, Yu Chun Lin, Pawel Niewiadomski, Benjamin Lin, Hideki Nakamura, Siew Cheng Phua, John Jiao, Andre Levchenko, Takafumi Inoue, Rajat Rohatgi

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    Primary cilia function as specialized compartments for signal transduction. The stereotyped structure and signaling function of cilia inextricably depend on the selective segregation of molecules in cilia. However, the fundamental principles governing the access of soluble proteins to primary cilia remain unresolved. We developed a methodology termed 'chemically inducible diffusion trap at cilia' to visualize the diffusion process of a series of fluorescent proteins ranging in size from 3.2 nm to 7.9 nm into primary cilia. We found that the interior of the cilium was accessible to proteins as large as 7.9 nm. The kinetics of ciliary accumulation of this panel of proteins was exponentially limited by their Stokes radii. Quantitative modeling suggests that the diffusion barrier operates as a molecular sieve at the base of cilia. Our study presents a set of powerful, generally applicable tools for the quantitative monitoring of ciliary protein diffusion under both physiological and pathological conditions

    Original languageEnglish
    Pages (from-to)437-443
    Number of pages7
    JournalNature Chemical Biology
    Volume9
    Issue number7
    DOIs
    Publication statusPublished - 2013 Jul

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    Cilia
    Proteins
    Signal Transduction

    ASJC Scopus subject areas

    • Cell Biology
    • Molecular Biology

    Cite this

    Inoue, T., Lin, Y. C., Niewiadomski, P., Lin, B., Nakamura, H., Phua, S. C., ... Rohatgi, R. (2013). Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier. Nature Chemical Biology, 9(7), 437-443. https://doi.org/10.1038/nchembio.1252

    Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier. / Inoue, Takanari; Lin, Yu Chun; Niewiadomski, Pawel; Lin, Benjamin; Nakamura, Hideki; Phua, Siew Cheng; Jiao, John; Levchenko, Andre; Inoue, Takafumi; Rohatgi, Rajat.

    In: Nature Chemical Biology, Vol. 9, No. 7, 07.2013, p. 437-443.

    Research output: Contribution to journalArticle

    Inoue, T, Lin, YC, Niewiadomski, P, Lin, B, Nakamura, H, Phua, SC, Jiao, J, Levchenko, A, Inoue, T & Rohatgi, R 2013, 'Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier', Nature Chemical Biology, vol. 9, no. 7, pp. 437-443. https://doi.org/10.1038/nchembio.1252
    Inoue T, Lin YC, Niewiadomski P, Lin B, Nakamura H, Phua SC et al. Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier. Nature Chemical Biology. 2013 Jul;9(7):437-443. https://doi.org/10.1038/nchembio.1252
    Inoue, Takanari ; Lin, Yu Chun ; Niewiadomski, Pawel ; Lin, Benjamin ; Nakamura, Hideki ; Phua, Siew Cheng ; Jiao, John ; Levchenko, Andre ; Inoue, Takafumi ; Rohatgi, Rajat. / Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier. In: Nature Chemical Biology. 2013 ; Vol. 9, No. 7. pp. 437-443.
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    abstract = "Primary cilia function as specialized compartments for signal transduction. The stereotyped structure and signaling function of cilia inextricably depend on the selective segregation of molecules in cilia. However, the fundamental principles governing the access of soluble proteins to primary cilia remain unresolved. We developed a methodology termed 'chemically inducible diffusion trap at cilia' to visualize the diffusion process of a series of fluorescent proteins ranging in size from 3.2 nm to 7.9 nm into primary cilia. We found that the interior of the cilium was accessible to proteins as large as 7.9 nm. The kinetics of ciliary accumulation of this panel of proteins was exponentially limited by their Stokes radii. Quantitative modeling suggests that the diffusion barrier operates as a molecular sieve at the base of cilia. Our study presents a set of powerful, generally applicable tools for the quantitative monitoring of ciliary protein diffusion under both physiological and pathological conditions",
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