Loss of Memo, a novel FGFR regulator, results in reduced lifespan

Area of Science:

• Cell Biology
• Molecular Biology
• Endocrinology

Background:

• Memo protein is crucial for cell motility induced by growth factors like heregulin (HRG), epidermal growth factor (EGF), and fibroblast growth factor (FGF).
• Its precise role downstream of fibroblast growth factor receptors (FGFRs) and its physiological functions remain largely undefined.

Purpose of the Study:

• To investigate the role of Memo protein in fibroblast growth factor receptor (FGFR) signaling pathways.
• To elucidate the physiological functions of Memo protein in vivo using a conditional knockout mouse model.

Main Methods:

• In vitro studies using mouse embryonic fibroblasts (wild-type or Memo knockout) to analyze Memo's association with the FGFR signalosome.
• Generation and analysis of conditional knockout mice lacking Memo to assess physiological consequences.

Main Results:

• Memo associates with the FGFR signalosome, indicating its necessity for optimal FGFR signaling activation.
• Memo-deficient mice exhibit a spectrum of phenotypes including reduced lifespan, small stature, metabolic changes (increased insulin sensitivity, fat loss), alopecia, kyphosis, and infertility.
• Memo-knockout mice display elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) and calcium, suggesting a role in vitamin D and calcium homeostasis.

Conclusions:

• Memo is a novel regulator of FGFR signaling, essential for normal cell motility and physiological homeostasis.
• The absence of Memo disrupts 1,25(OH)2D production and calcium regulation, leading to significant health impairments in vivo.