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Endocytosis as a stabilizing mechanism for tissue homeostasis

Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in whi...

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Autores principales: Adler, Miri, Mayo, Avi, Zhou, Xu, Franklin, Ruth A., Jacox, Jeremy B., Medzhitov, Ruslan, Alon, Uri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828590/
https://www.ncbi.nlm.nih.gov/pubmed/29429964
http://dx.doi.org/10.1073/pnas.1714377115
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author Adler, Miri
Mayo, Avi
Zhou, Xu
Franklin, Ruth A.
Jacox, Jeremy B.
Medzhitov, Ruslan
Alon, Uri
author_facet Adler, Miri
Mayo, Avi
Zhou, Xu
Franklin, Ruth A.
Jacox, Jeremy B.
Medzhitov, Ruslan
Alon, Uri
author_sort Adler, Miri
collection PubMed
description Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in which cells stimulate each other and grow without control. Feedback can be obtained in at least two ways: endocytosis in which a cell removes its cognate GF by internalization and cross-inhibition in which a GF down-regulates the production of another GF. Here we ask whether there are design principles for cell circuits to achieve tissue homeostasis. We develop an analytically solvable framework for circuits with multiple cell types and find that feedback by endocytosis is far more robust to parameter variation and has faster responses than cross-inhibition. Endocytosis, which is found ubiquitously across tissues, can even provide homeostasis to three and four communicating cell types. These design principles form a conceptual basis for how tissues maintain a healthy balance of cell types and how balance may be disrupted in diseases such as degeneration and fibrosis.
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spelling pubmed-58285902018-02-28 Endocytosis as a stabilizing mechanism for tissue homeostasis Adler, Miri Mayo, Avi Zhou, Xu Franklin, Ruth A. Jacox, Jeremy B. Medzhitov, Ruslan Alon, Uri Proc Natl Acad Sci U S A PNAS Plus Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in which cells stimulate each other and grow without control. Feedback can be obtained in at least two ways: endocytosis in which a cell removes its cognate GF by internalization and cross-inhibition in which a GF down-regulates the production of another GF. Here we ask whether there are design principles for cell circuits to achieve tissue homeostasis. We develop an analytically solvable framework for circuits with multiple cell types and find that feedback by endocytosis is far more robust to parameter variation and has faster responses than cross-inhibition. Endocytosis, which is found ubiquitously across tissues, can even provide homeostasis to three and four communicating cell types. These design principles form a conceptual basis for how tissues maintain a healthy balance of cell types and how balance may be disrupted in diseases such as degeneration and fibrosis. National Academy of Sciences 2018-02-20 2018-02-02 /pmc/articles/PMC5828590/ /pubmed/29429964 http://dx.doi.org/10.1073/pnas.1714377115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Adler, Miri
Mayo, Avi
Zhou, Xu
Franklin, Ruth A.
Jacox, Jeremy B.
Medzhitov, Ruslan
Alon, Uri
Endocytosis as a stabilizing mechanism for tissue homeostasis
title Endocytosis as a stabilizing mechanism for tissue homeostasis
title_full Endocytosis as a stabilizing mechanism for tissue homeostasis
title_fullStr Endocytosis as a stabilizing mechanism for tissue homeostasis
title_full_unstemmed Endocytosis as a stabilizing mechanism for tissue homeostasis
title_short Endocytosis as a stabilizing mechanism for tissue homeostasis
title_sort endocytosis as a stabilizing mechanism for tissue homeostasis
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828590/
https://www.ncbi.nlm.nih.gov/pubmed/29429964
http://dx.doi.org/10.1073/pnas.1714377115
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