Small integral membrane protein 10 like 1 downregulation enhances differentiation of adipose progenitor cells.

Abstract

Small integral membrane protein 10 like 1 (SMIM10L1) was identified by RNA sequencing as the most significantly downregulated gene in Phosphatase and Tensin Homologue (PTEN) knockdown adipose progenitor cells (APCs). PTEN is a tumor suppressor that antagonizes the growth promoting Phosphoinositide 3-kinase (PI3K)/AKT/mechanistic Target of Rapamycin (mTOR) cascade. Diseases caused by germline pathogenic variants in PTEN are summarized as PTEN Hamartoma Tumor Syndrome (PHTS). This overgrowth syndrome is associated with lipoma formation, especially in pediatric patients. The mechanisms underlying this adipose tissue dysfunction remain elusive. We observed that SMIM10L1 downregulation in APCs led to an enhanced adipocyte differentiation in two- and three-dimensional cell culture and increased expression of adipogenesis markers. Furthermore, SMIM10L1 knockdown cells showed a decreased expression of PTEN, pointing to a mutual crosstalk between PTEN and SMIM10L1. In line with these observations, SMIM10L1 knockdown cells showed increased activation of PI3K/AKT/mTOR signaling and concomitantly increased expression of the adipogenic transcription factor SREBP1. We computationally predicted an α-helical structure and membrane association of SMIM10L1. These results support a specific role for SMIM10L1 in regulating adipogenesis, potentially by increasing PI3K/AKT/mTOR signaling, which might be conducive to lipoma formation in pediatric patients with PHTS.

• Authors: Michèle Nebe, Stephanie Kehr, Samuel Schmitz, Jana Breitfeld, Judith Lorenz, Diana Le Duc, Peter F Stadler, Jens Meiler, Wieland Kiess, Antje Garten, Anna S Kirstein
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 604 Pg. 57-62 (05 14 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35290761 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Membrane Proteins
• Phosphatidylinositol 3-Kinase
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• TOR Serine-Threonine Kinases
• SMIM10L1 protein, human

Topics

• Child
• Humans
• Adipocytes (metabolism)
• Adipose Tissue (metabolism)
• Down-Regulation
• Hamartoma Syndrome, Multiple (genetics)
• Lipoma (metabolism)
• Membrane Proteins (genetics, metabolism)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• PTEN Phosphohydrolase (genetics, metabolism)
• Stem Cells (metabolism)
• TOR Serine-Threonine Kinases (metabolism)