The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

Johanna Lena Schön; Victoria Elisabeth Groß; Willem Berend Post; Alexandra Daum; Daniel Matúš; Johanna Pilz; Rene Schnorr; Susanne Horn; Miriam Bäumers; Stefanie Weidtkamp-Peters; Samantha Hughes; Torsten Schöneberg; Simone Prömel

doi:10.1016/j.matbio.2024.02.005

The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

Johanna Lena Schön, Victoria Elisabeth Groß, Willem Berend Post, Alexandra Daum, Daniel Matúš, Johanna Pilz, Rene Schnorr, Susanne Horn, Miriam Bäumers, Stefanie Weidtkamp-Peters, Samantha Hughes, Torsten Schöneberg, Simone Prömel^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms. Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode Caenorhabditis elegans, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (trans) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Matrix Biology
Volume	128
Early online date	18 Feb 2024
DOIs	https://doi.org/10.1016/j.matbio.2024.02.005
Publication status	Published - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024

Funding

The authors thank Harald Hutter and Ralf Schnabel for kindly providing plasmids and Harald Hutter and Shohei Mitani for sharing C. elegans strains. They are grateful to the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), for C. elegans strains. This work was supported by scholarships to J.L.S. and D.M. from the Medical Faculty, Leipzig University, and grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through CRC 1208 (project number 267205415, B14 (S.P.), Z02 (M.B. and S.W.P.)), CRC 1423 (project number 421152132, B06 (T.S.)), and funding for the instrumentation Leica TCS SP8 STED 3X (DFG- INST 208/665–1 FUGG). The authors thank Harald Hutter and Ralf Schnabel for kindly providing plasmids and Harald Hutter and Shohei Mitani for sharing C. elegans strains. They are grateful to the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), for C. elegans strains. They would also like to acknowledge the Center for Advanced Imaging (CAi) at the Heinrich-Heine-University Düsseldorf for providing access to the Leica TCS SP8 STED 3X (DFG- INST 208/665–1 FUGG). This work was supported by scholarships to J.L.S. and D.M. from the Medical Faculty, Leipzig University, and grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through CRC 1208 (project number 267205415, B14 (S.P.), Z02 (M.B. and S.W.P.)), CRC 1423 (project number 421152132, B06 (T.S.)), and funding for the instrumentation Leica TCS SP8 STED 3X (DFG- INST 208/665–1 FUGG).

Funders	Funder number
Harald Hutter and Ralf Schnabel
National Institutes of Health	P40 OD010440
Center for Advanced Brain Imaging	DFG- INST 208/665–1 FUGG
Deutsche Forschungsgemeinschaft	267205415, 421152132, CRC 1208

Keywords

Adhesion GPCR
Body size
Extracellular matrix
Flamingo/CELSR
Planar cell polarity

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10.1016/j.matbio.2024.02.005

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Schön, J. L., Groß, V. E., Post, W. B., Daum, A., Matúš, D., Pilz, J., Schnorr, R., Horn, S., Bäumers, M., Weidtkamp-Peters, S., Hughes, S., Schöneberg, T., & Prömel, S. (2024). The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix. Matrix Biology, 128, 1-10. https://doi.org/10.1016/j.matbio.2024.02.005

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abstract = "The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms. Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode Caenorhabditis elegans, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (trans) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.",

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Schön, JL, Groß, VE, Post, WB, Daum, A, Matúš, D, Pilz, J, Schnorr, R, Horn, S, Bäumers, M, Weidtkamp-Peters, S, Hughes, S, Schöneberg, T & Prömel, S 2024, 'The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix', Matrix Biology, vol. 128, pp. 1-10. https://doi.org/10.1016/j.matbio.2024.02.005

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T1 - The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

AU - Schön, Johanna Lena

AU - Groß, Victoria Elisabeth

AU - Post, Willem Berend

AU - Daum, Alexandra

AU - Matúš, Daniel

AU - Pilz, Johanna

AU - Schnorr, Rene

AU - Horn, Susanne

AU - Bäumers, Miriam

AU - Weidtkamp-Peters, Stefanie

AU - Hughes, Samantha

AU - Schöneberg, Torsten

AU - Prömel, Simone

PY - 2024/4

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N2 - The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms. Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode Caenorhabditis elegans, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (trans) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.

AB - The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms. Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode Caenorhabditis elegans, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (trans) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.

KW - Adhesion GPCR

KW - Body size

KW - Extracellular matrix

KW - Flamingo/CELSR

KW - Planar cell polarity

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ER -

The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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