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

Lidia Hernandez; Kyle J. Roux; Esther Sook Miin Wong; Leslie C. Mounkes; Rafidah Mutalif; Raju Navasankari; Bina Rai; Simon Cool; Jae Wook Jeong; Honghe Wang; Hyun Shik Lee; Serguei Kozlov; Martin Grunert; Thomas Keeble; C. Michael Jones; Margarita D. Meta; Stephen G. Young; Ira O. Daar; Brian Burke; Alan O. Perantoni; Colin L. Stewart

doi:10.1016/j.devcel.2010.08.013

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

Lidia Hernandez, Kyle J. Roux, Esther Sook Miin Wong, Leslie C. Mounkes, Rafidah Mutalif, Raju Navasankari, Bina Rai, Simon Cool, Jae Wook Jeong, Honghe Wang, Hyun Shik Lee, Serguei Kozlov, Martin Grunert, Thomas Keeble, C. Michael Jones, Margarita D. Meta, Stephen G. Young, Ira O. Daar, Brian Burke, Alan O. PerantoniColin L. Stewart

Research output: Contribution to journal › Article › peer-review

149 Scopus citations

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.

Original language	English
Pages (from-to)	413-425
Number of pages	13
Journal	Developmental Cell
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.devcel.2010.08.013
State	Published - Sep 2010

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Hernandez, L., Roux, K. J., Wong, E. S. M., Mounkes, L. C., Mutalif, R., Navasankari, R., Rai, B., Cool, S., Jeong, J. W., Wang, H., Lee, H. S., Kozlov, S., Grunert, M., Keeble, T., Jones, C. M., Meta, M. D., Young, S. G., Daar, I. O., Burke, B., ... Stewart, C. L. (2010). Functional coupling between the extracellular matrix and nuclear lamina by wnt signaling in progeria. Developmental Cell, 19(3), 413-425. https://doi.org/10.1016/j.devcel.2010.08.013

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title = "Functional coupling between the extracellular matrix and nuclear lamina by wnt signaling in progeria",

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.",

author = "Lidia Hernandez and Roux, {Kyle J.} and Wong, {Esther Sook Miin} and Mounkes, {Leslie C.} and Rafidah Mutalif and Raju Navasankari and Bina Rai and Simon Cool and Jeong, {Jae Wook} and Honghe Wang and Lee, {Hyun Shik} and Serguei Kozlov and Martin Grunert and Thomas Keeble and Jones, {C. Michael} and Meta, {Margarita D.} and Young, {Stephen G.} and Daar, {Ira O.} and Brian Burke and Perantoni, {Alan O.} and Stewart, {Colin L.}",

year = "2010",

month = sep,

doi = "10.1016/j.devcel.2010.08.013",

language = "English",

volume = "19",

pages = "413--425",

journal = "Developmental Cell",

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Hernandez, L, Roux, KJ, Wong, ESM, 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 2010, 'Functional coupling between the extracellular matrix and nuclear lamina by wnt signaling in progeria', Developmental Cell, vol. 19, no. 3, pp. 413-425. https://doi.org/10.1016/j.devcel.2010.08.013

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AU - Hernandez, Lidia

AU - Roux, Kyle J.

AU - Wong, Esther Sook Miin

AU - Mounkes, Leslie C.

AU - Mutalif, Rafidah

AU - Navasankari, Raju

AU - Rai, Bina

AU - Cool, Simon

AU - Jeong, Jae Wook

AU - Wang, Honghe

AU - Lee, Hyun Shik

AU - Kozlov, Serguei

AU - Grunert, Martin

AU - Keeble, Thomas

AU - Jones, C. Michael

AU - Meta, Margarita D.

AU - Young, Stephen G.

AU - Daar, Ira O.

AU - Burke, Brian

AU - Perantoni, Alan O.

AU - Stewart, Colin L.

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

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SN - 1534-5807

VL - 19

SP - 413

EP - 425

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -

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

Abstract

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