XB-ART-42278
Dev Cell
2010 Sep 14;193:413-25. doi: 10.1016/j.devcel.2010.08.013.
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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
.
???displayArticle.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.
???displayArticle.pubmedLink??? 20833363
???displayArticle.pmcLink??? PMC2953243
???displayArticle.link??? Dev Cell
???displayArticle.grants??? [+]
R01HD057873 NICHD NIH HHS , Z01 BC005093-29 NCI NIH HHS , R01 AG035626-09 NIA NIH HHS , R01 AG035626 NIA NIH HHS , Z01 BC005093-29 Intramural NIH HHS, R01 HD057873 NICHD NIH HHS
Species referenced: Xenopus laevis
Genes referenced: lef1 lmna robo3 tcf4 wnt3a
GO keywords: extracellular matrix [+]
???displayArticle.antibodies??? Lmna Ab1 Tcf3 Ab3
???displayArticle.disOnts??? progeria
???displayArticle.omims??? HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
???attribute.lit??? ???displayArticles.show???
Figure 5. δ9 and δ50 Lamin Inhibit Wnt-Mediated Transcription(A) TOPflash/FOPflash luciferase reporter assays with WT (BC), δ9, δ50 lamins, or their SSIM variants.(B) Gst-Tcf pull-down of nuclear β-catenin levels.(C) Injection of Xwnt3a mRNA into Xenopus embryos, alone or in the presence of each LMNA construct shown in (A) and (B). Lower panel, western analysis shows amount of protein derived from the different LMNA mRNAs injected.Error bars are SEM. |
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