Dataset Information

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.

SUBMITTER: Hernandez L

PROVIDER: S-EPMC2953243 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Hernandez Lidia L Roux Kyle J KJ Wong Esther Sook Miin ES Mounkes Leslie C LC Mutalif Rafidah R Navasankari Raju R Rai Bina B Cool Simon S Jeong Jae-Wook JW Wang Honghe H Lee Hyun-Shik HS Kozlov Serguei S Grunert Martin M Keeble Thomas T Jones C Michael CM Meta Margarita D MD Young Stephen G SG Daar Ira O IO Burke Brian B Perantoni Alan O AO Stewart Colin L CL

Developmental cell 20100901 3

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 ...[more]

PMID: 20833363

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Project description:Nuclear matrix constituent proteins in plants function like animal lamins, providing the structural foundation of the nuclear lamina and regulating nuclear organization and morphology. Although they are well characterized in angiosperms, the presence and structure of nuclear matrix constituent proteins in more distantly related species, such as streptophytic algae, are relatively unknown. The rapid evolution of nuclear matrix constituent proteins throughout the plant lineage has caused a divergence in protein sequence that makes similarity-based searches less effective. Structural features are more likely to be conserved compared to primary amino acid sequence; therefore, we developed a filtration protocol to search for diverged nuclear matrix constituent proteins based on four physical characteristics: intrinsically disordered content, isoelectric point, number of amino acids, and the presence of a central coiled-coil domain. By setting parameters to recognize the properties of bona fide nuclear matrix constituent protein proteins in angiosperms, we filtered eight complete proteomes from streptophytic algae species and identified strong nuclear matrix constituent protein candidates in six taxa in the Classes Zygnematophyceae, Charophyceae, and Klebsormidiophyceae. Through analysis of these proteins, we observed structural variance in domain size between nuclear matrix constituent proteins in algae and land plants, as well as a single block of amino acid conservation. Our analysis indicates that nuclear matrix constituent proteins are absent in the Mesostigmatophyceae. The presence versus absence of nuclear matrix constituent protein proteins does not correlate with the distribution of different forms of mitosis (e.g. closed/semi-closed/open) but does correspond to the transition from unicellularity to multicellularity in the streptophytic algae, suggesting that a nuclear matrix constituent protein-based nucleoskeleton plays important roles in supporting cell-to-cell interactions.

Dataset Information

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

Publications

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

Similar Datasets

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