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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: Boog, Hendrik, Medda, Rebecca, Cavalcanti-Adam, Elisabetta Ada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620704/
https://www.ncbi.nlm.nih.gov/pubmed/34821850
http://dx.doi.org/10.3390/jimaging7110219
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author Boog, Hendrik
Medda, Rebecca
Cavalcanti-Adam, Elisabetta Ada
author_facet Boog, Hendrik
Medda, Rebecca
Cavalcanti-Adam, Elisabetta Ada
author_sort Boog, Hendrik
collection PubMed
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.
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spelling pubmed-86207042021-11-27 Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions Boog, Hendrik Medda, Rebecca Cavalcanti-Adam, Elisabetta Ada J Imaging Article 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. MDPI 2021-10-20 /pmc/articles/PMC8620704/ /pubmed/34821850 http://dx.doi.org/10.3390/jimaging7110219 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boog, Hendrik
Medda, Rebecca
Cavalcanti-Adam, Elisabetta Ada
Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620704/
https://www.ncbi.nlm.nih.gov/pubmed/34821850
http://dx.doi.org/10.3390/jimaging7110219
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