Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane...

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Autores principales: Hendrik Boog, Rebecca Medda, Elisabetta Ada Cavalcanti-Adam
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/c07988f881b74d929b21bd07ef869e74
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spelling oai:doaj.org-article:c07988f881b74d929b21bd07ef869e742021-11-25T18:03:22ZSingle Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions10.3390/jimaging71102192313-433Xhttps://doaj.org/article/c07988f881b74d929b21bd07ef869e742021-10-01T00:00:00Zhttps://www.mdpi.com/2313-433X/7/11/219https://doaj.org/toc/2313-433XAt the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenetic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as preformed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allow not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs might occur. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.Hendrik BoogRebecca MeddaElisabetta Ada Cavalcanti-AdamMDPI AGarticlereceptor complexdistributioncenter of masscell shapePhotographyTR1-1050Computer applications to medicine. Medical informaticsR858-859.7Electronic computers. Computer scienceQA75.5-76.95ENJournal of Imaging, Vol 7, Iss 219, p 219 (2021)
institution DOAJ
collection DOAJ
language EN
topic receptor complex
distribution
center of mass
cell shape
Photography
TR1-1050
Computer applications to medicine. Medical informatics
R858-859.7
Electronic computers. Computer science
QA75.5-76.95
spellingShingle receptor complex
distribution
center of mass
cell shape
Photography
TR1-1050
Computer applications to medicine. Medical informatics
R858-859.7
Electronic computers. Computer science
QA75.5-76.95
Hendrik Boog
Rebecca Medda
Elisabetta Ada Cavalcanti-Adam
Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
description At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenetic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as preformed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allow not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs might occur. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.
format article
author Hendrik Boog
Rebecca Medda
Elisabetta Ada Cavalcanti-Adam
author_facet Hendrik Boog
Rebecca Medda
Elisabetta Ada Cavalcanti-Adam
author_sort Hendrik Boog
title Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title_short Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title_full Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title_fullStr Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title_full_unstemmed Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title_sort single cell center of mass for the analysis of bmp receptor heterodimers distributions
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/c07988f881b74d929b21bd07ef869e74
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