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doi:10.22028/D291-35105
Titel: | Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant |
VerfasserIn: | Fecher-Trost, Claudia Wolske, Karin Wesely, Christine Löhr, Heidi Klawitter, Daniel S. Weissgerber, Petra Gradhand, Elise Burren, Christine P. Mason, Anna E. Winter, Manuel Wissenbach, Ulrich |
Sprache: | Englisch |
Titel: | International Journal of Molecular Sciences |
Bandnummer: | 22 |
Heft: | 23 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | TRPV6 placenta calcium transport skeletal dysplasia serine proteases subunit assembly transient receptor potential |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R510stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G660R) that, surprisingly, does not affect the Ca2+ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G660R and R510stop mutants and combinations with wild type TRPV6. We show that both the G660R and R510stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases. |
DOI der Erstveröffentlichung: | 10.3390/ijms222312694 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-351056 hdl:20.500.11880/32138 http://dx.doi.org/10.22028/D291-35105 |
ISSN: | 1422-0067 |
Datum des Eintrags: | 6-Jan-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Material |
In Beziehung stehendes Objekt: | https://www.mdpi.com/1422-0067/22/23/12694/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Experimentelle und Klinische Pharmakologie und Toxikologie |
Professur: | M - Prof. Dr. Veit Flockerzi |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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ijms-22-12694.pdf | 2,47 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons