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BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis
BMP7/BMP2 or BMP7/BMP4 heterodimers are more active than homodimers in vitro, but it is not known whether these heterodimers signal in vivo. To test this, we generated knock in mice carrying a mutation (Bmp7(R-GFlag)) that prevents proteolytic activation of the dimerized BMP7 precursor protein. This...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785266/ https://www.ncbi.nlm.nih.gov/pubmed/31566563 http://dx.doi.org/10.7554/eLife.48872 |
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author | Kim, Hyung-Seok Neugebauer, Judith McKnite, Autumn Tilak, Anup Christian, Jan L |
author_facet | Kim, Hyung-Seok Neugebauer, Judith McKnite, Autumn Tilak, Anup Christian, Jan L |
author_sort | Kim, Hyung-Seok |
collection | PubMed |
description | BMP7/BMP2 or BMP7/BMP4 heterodimers are more active than homodimers in vitro, but it is not known whether these heterodimers signal in vivo. To test this, we generated knock in mice carrying a mutation (Bmp7(R-GFlag)) that prevents proteolytic activation of the dimerized BMP7 precursor protein. This mutation eliminates the function of BMP7 homodimers and all other BMPs that normally heterodimerize with BMP7. While Bmp7 null homozygotes are live born, Bmp7(R-GFlag) homozygotes are embryonic lethal and have broadly reduced BMP activity. Furthermore, compound heterozygotes carrying the Bmp7(R-G) allele together with a null allele of Bmp2 or Bmp4 die during embryogenesis with defects in ventral body wall closure and/or the heart. Co-immunoprecipitation assays confirm that endogenous BMP4/7 heterodimers exist. Thus, BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian development, which may explain why mutations in either Bmp4 or Bmp7 lead to a similar spectrum of congenital defects in humans. |
format | Online Article Text |
id | pubmed-6785266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-67852662019-10-10 BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis Kim, Hyung-Seok Neugebauer, Judith McKnite, Autumn Tilak, Anup Christian, Jan L eLife Cell Biology BMP7/BMP2 or BMP7/BMP4 heterodimers are more active than homodimers in vitro, but it is not known whether these heterodimers signal in vivo. To test this, we generated knock in mice carrying a mutation (Bmp7(R-GFlag)) that prevents proteolytic activation of the dimerized BMP7 precursor protein. This mutation eliminates the function of BMP7 homodimers and all other BMPs that normally heterodimerize with BMP7. While Bmp7 null homozygotes are live born, Bmp7(R-GFlag) homozygotes are embryonic lethal and have broadly reduced BMP activity. Furthermore, compound heterozygotes carrying the Bmp7(R-G) allele together with a null allele of Bmp2 or Bmp4 die during embryogenesis with defects in ventral body wall closure and/or the heart. Co-immunoprecipitation assays confirm that endogenous BMP4/7 heterodimers exist. Thus, BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian development, which may explain why mutations in either Bmp4 or Bmp7 lead to a similar spectrum of congenital defects in humans. eLife Sciences Publications, Ltd 2019-09-30 /pmc/articles/PMC6785266/ /pubmed/31566563 http://dx.doi.org/10.7554/eLife.48872 Text en © 2019, Kim et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Kim, Hyung-Seok Neugebauer, Judith McKnite, Autumn Tilak, Anup Christian, Jan L BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title | BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title_full | BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title_fullStr | BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title_full_unstemmed | BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title_short | BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis |
title_sort | bmp7 functions predominantly as a heterodimer with bmp2 or bmp4 during mammalian embryogenesis |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785266/ https://www.ncbi.nlm.nih.gov/pubmed/31566563 http://dx.doi.org/10.7554/eLife.48872 |
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