Phospholipid scramblase 4 (PLSCR4) is a member of a conserved enzyme family with
high relevance for the remodeling of phospholipid distribution in the plasma membrane and the
regulation of cellular signaling. While PLSCR1 and -3 are involved in the regulation of adipose-tissue
expansion, the role of PLSCR4 is so far unknown. PLSCR4 is significantly downregulated in an
adipose-progenitor-cell model of deficiency for phosphatase and tensin homolog (PTEN). PTEN
acts as a tumor suppressor and antagonist of the growth and survival signaling phosphoinositide
3-kinase (PI3K)/AKT cascade by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3).
Patients with PTEN germline deletion frequently develop lipomas. The underlying mechanism for
this aberrant adipose-tissue growth is incompletely understood. PLSCR4 is most highly expressed in
human adipose tissue, compared with other phospholipid scramblases, suggesting a specific role
of PLSCR4 in adipose-tissue biology. In cell and mouse models of lipid accumulation, we found
PLSCR4 to be downregulated. We observed increased adipogenesis in PLSCR4-knockdown adipose
progenitor cells, while PLSCR4 overexpression attenuated lipid accumulation. PLSCR4 knockdown
was associated with increased PIP3 levels and the activation of AKT. Our results indicated that
PLSCR4 is a regulator of PI3K/AKT signaling and adipogenesis and may play a role in PTENassociated adipose-tissue overgrowth and lipoma formation.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88461 |
| Date | 05 December 2023 |
| Creators | A. G. Barth, Lisa, Nebe, Michèle, Kalwa, Hermann, Velluva, Akhil, Kehr, Stephanie, Kolbig, Florentien, Prabutzki, Patricia, Kiess, Wieland, Le Duc, Diana, Garten, Antje, S. Kirstein, Anna |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1422-0067, 10.3390/ijms23179787 |
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