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XB-ART-42278
Dev Cell September 14, 2010; 19 (3): 413-25.

Functional coupling between the extracellular matrix and nuclear lamina by Wnt signaling in progeria.

Hernandez L , Roux KJ , Wong ES , Mounkes LC , Mutalif R , Navasankari R , Rai B , Cool S , Jeong JW , Wang H , Lee HS , Kozlov S , Grunert M , Keeble T , Jones CM , Meta MD , Young SG , Daar IO , Burke B , Perantoni AO , Stewart CL .


Abstract
The segmental premature aging disease Hutchinson-Gilford Progeria (HGPS) is caused by a truncated and farnesylated form of Lamin A. In a mouse model for HGPS, a similar Lamin A variant causes the proliferative arrest and death of postnatal, but not embryonic, fibroblasts. Arrest is due to an inability to produce a functional extracellular matrix (ECM), because growth on normal ECM rescues proliferation. The defects are associated with inhibition of canonical Wnt signaling, due to reduced nuclear localization and transcriptional activity of Lef1, but not Tcf4, in both mouse and human progeric cells. Defective Wnt signaling, affecting ECM synthesis, may be critical to the etiology of HGPS because mice exhibit skeletal defects and apoptosis in major blood vessels proximal to the heart. These results establish a functional link between the nuclear envelope/lamina and the cell surface/ECM and may provide insights into the role of Wnt signaling and the ECM in aging.

PubMed ID: 20833363
PMC ID: PMC2953243
Article link: Dev Cell
Grant support: [+]
Genes referenced: lef1 lmna robo3 tcf4
GO keywords: extracellular matrix [+]
Antibodies: Lmna Ab1 Tcf3 Ab3

Disease Ontology terms: progeria
OMIMs: HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS

Article Images: [+] show captions
References [+] :
Adams, Regulation of development and differentiation by the extracellular matrix. 1993, Pubmed


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