SSBD:database

Project ID

412-Katoh-BMP4Cilia

Project SID

412

Title

BMP4 regulates asymmetric Pkd2 distribution in mouse nodal immotile cilia and ciliary mechanosensing required for left–right determination

Description

Background: Mouse nodal immotile cilia mechanically sense the bending direction for left–right (L–R) determination and activate the left-side-specific signaling cascade, leading to increased Nodal activity. Asymmetric distribution of Pkd2, a crucial channel for L–R determination, on immotile cilia has been reported recently. However, the causal relationship between the asymmetric Pkd2 distribution and direction-dependent flow sensing is not well understood. Furthermore, the underlying molecular mechanism directing this asymmetric Pkd2 distribution remains unclear. Results: The effects of several recombinant proteins and inhibitors on the Pkd2 distribution were analyzed using super-resolution microscopy. Notably, bone morphogenetic protein 4 (BMP4) affected the Pkd2 distribution. Addi- tionally, three-dimensional manipulation of nodal immotile cilia using optical tweezers revealed that excess BMP4 caused defects in the mechanosensing abil- ity of the cilia. Conclusions: Experimental data together with model calculations suggest that BMP4 regulates the asymmetric distribution of Pkd2 in nodal immotile cilia, thereby affecting the ability of these cilia to sense the bending direction for L– R determination. This study, for the first time, provides insight into the rela- tionship between the asymmetric protein distribution in cilia and their function.

Submission Date

2025-01-27

Opened Date

-

Release Date

2025-11-28

Update Date

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Kind

License

Project URL

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Project DOI

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Metadata Version

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Template Version

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Funding Information

This study was supported by the FOREST Program (grant no. JPMJFR224N) of the Japan Science and Technology Agency (JST), Grant-in-Aid (grant no. 21K15096, 24K18107, and 24H01270) from the Japan Society for the Promotion of Science (JSPS), RIKEN Special Postdoctoral Researcher Pro- gram, The University of Tokyo Excellent Young Researcher Program, Ultrastructure Research Fund from The Japanese Society of Microscopy to T.A.K.; by a grant from the Japan Society for the Promotion of Science (no. 17H01435) to H.H.; by JSPS grants 19H05794, 19H05795 and 22H04926; JST grants JPMJMS2025-14, JPMJCR20E2 to Y.O. This work was supported in part by the University of Tokyo Research Internship Program (UTRIP) 2023 to Y.O.

Total

77 files / 140.7 GB

Image datasets

zipped 20 files / 21.5 GB, raw image 24 files / 48.9 GB, total 44 files / 70.4 GB

Quantitative datasets

zipped 0 files / 0 bytes, raw bdml 0 files / 0 bytes, total 0 files / 0 bytes

Organism

Strain

Cell

Cell line

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MeSH

Anatomical Entity

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UBERON

Biological Process

Cellular Component

Molecular Function

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Medical Subject Headings

Method involved in biological imaging