TY - JOUR
T1 - Loss of Memo, a novel FGFR regulator, results in reduced lifespan
AU - Haenzi, Barbara
AU - Bonny, Olivier
AU - Masson, Régis
AU - Lienhard, Susanne
AU - Dey, Julien H.
AU - Kuro-O, Makoto
AU - Hynes, Nancy E.
PY - 2014/1
Y1 - 2014/1
N2 - Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)2D production and normal calcium homeostasis.
AB - Memo is a widely expressed 33-kDa protein required for heregulin (HRG)-, epidermal growth factor (EGF)-, and fibroblast growth factor (FGF)-induced cell motility. Studies in mouse embryonic fibroblasts, wild-type or knockout for Memo, were performed to further investigate the role of Memo downstream of FGFR. We demonstrated that Memo associates with the FGFR signalosome and is necessary for optimal activation of signaling. To uncover Memo's physiological role, Memo conditional-knockout mice were generated. These animals showed a reduced life span, increased insulin sensitivity, small stature, graying hair, alopecia, kyphosis, loss of subcutaneous fat, and loss of spermatozoa in the epididymis. Memo-knockout mice also have elevated serum levels of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), and calcium compared to control littermates expressing Memo. In summary, the results from in vivo and in vitro models support the hypothesis that Memo is a novel regulator of FGFR signaling with a role in controlling 1,25(OH)2D production and normal calcium homeostasis.
KW - Calcium
KW - Insulin sensitivity
KW - Kidney
KW - Mineral homeostasis
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=84894517515&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894517515&partnerID=8YFLogxK
U2 - 10.1096/fj.13-228320
DO - 10.1096/fj.13-228320
M3 - Article
C2 - 24056085
AN - SCOPUS:84894517515
SN - 0892-6638
VL - 28
SP - 327
EP - 336
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -