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The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration
Testicans are modular proteoglycans of the extracellular matrix of various tissues where they contribute to matrix integrity and exert cellular effects like neurite outgrowth and cell migration. Using testican-2 as a representative member of the family, we tackle the complete lack of general structu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763218/ https://www.ncbi.nlm.nih.gov/pubmed/33321927 http://dx.doi.org/10.3390/ijms21249413 |
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author | Krajnc, Anja Gaber, Aljaž Lenarčič, Brigita Pavšič, Miha |
author_facet | Krajnc, Anja Gaber, Aljaž Lenarčič, Brigita Pavšič, Miha |
author_sort | Krajnc, Anja |
collection | PubMed |
description | Testicans are modular proteoglycans of the extracellular matrix of various tissues where they contribute to matrix integrity and exert cellular effects like neurite outgrowth and cell migration. Using testican-2 as a representative member of the family, we tackle the complete lack of general structural information and structure–function relationship. First, we show using isothermal titration calorimetry and modeling that extracellular calcium-binding domain (EC) has only one active calcium-binding site, while the other potential site is inactive, and that testican-2 is within extracellular matrix always in the calcium-loaded form. Next, we demonstrate using various prediction methods that N- and C-terminal regions plus interdomain connections are flexible. We support this by small-angle X-ray-scattering analysis of C-terminally truncated testican-2, which indicates that the triplet follistatin-EC-thyroglobulin domain forms a moderately compact core while the unique N-terminal is disordered. Finally, using cell exclusion zone assay, we show that it is this domain triplet that is responsible for promoting cell migration and not the N- and C-terminal regions. |
format | Online Article Text |
id | pubmed-7763218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77632182020-12-27 The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration Krajnc, Anja Gaber, Aljaž Lenarčič, Brigita Pavšič, Miha Int J Mol Sci Article Testicans are modular proteoglycans of the extracellular matrix of various tissues where they contribute to matrix integrity and exert cellular effects like neurite outgrowth and cell migration. Using testican-2 as a representative member of the family, we tackle the complete lack of general structural information and structure–function relationship. First, we show using isothermal titration calorimetry and modeling that extracellular calcium-binding domain (EC) has only one active calcium-binding site, while the other potential site is inactive, and that testican-2 is within extracellular matrix always in the calcium-loaded form. Next, we demonstrate using various prediction methods that N- and C-terminal regions plus interdomain connections are flexible. We support this by small-angle X-ray-scattering analysis of C-terminally truncated testican-2, which indicates that the triplet follistatin-EC-thyroglobulin domain forms a moderately compact core while the unique N-terminal is disordered. Finally, using cell exclusion zone assay, we show that it is this domain triplet that is responsible for promoting cell migration and not the N- and C-terminal regions. MDPI 2020-12-10 /pmc/articles/PMC7763218/ /pubmed/33321927 http://dx.doi.org/10.3390/ijms21249413 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Krajnc, Anja Gaber, Aljaž Lenarčič, Brigita Pavšič, Miha The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title | The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title_full | The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title_fullStr | The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title_full_unstemmed | The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title_short | The Central Region of Testican-2 Forms a Compact Core and Promotes Cell Migration |
title_sort | central region of testican-2 forms a compact core and promotes cell migration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763218/ https://www.ncbi.nlm.nih.gov/pubmed/33321927 http://dx.doi.org/10.3390/ijms21249413 |
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