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Actin-SRF Signaling in the Developing and Mature Murine Brain

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Two Faces of Evil: Cancer and Neurodegeneration

Part of the book series: Research and Perspectives in Alzheimer's Disease ((ALZHEIMER))

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Abstract

Functional characterization of the transcription factor Serum Response Factor (SRF) has generated new insight into cellular mechanisms by which the actin cytoskeletal microfilament communicates with the genome. In essence, the SRF cofactors of the Myocardin Related Transcription Factor (MRTF) protein family sense cytoplasmic G-actin levels such that, upon stimulated F-actin polymerization, MRTFs translocate to the nucleus. This translocation leads to activated transcription of SRF target genes, a subset of which encodes actin and other cytoskeletal proteins. Migratory activities of cells are modulated thereby, including motile functions of neurons and metastatic cancer cells. In the mouse brain, SRF-directed gene expression contributes to both embryonic and adult activities. Essential neuronal migratory events of pre- and postnatal brain development are impaired in SRF-deficient mouse mutants. Furthermore, in the mature brain, essential cognitive functions, including learning and memory, are critically dependent upon SRF and its MRTF cofactors.

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Acknowledgments

AN acknowledges financial support from the DFG through grant NO 120/12-3. BK is supported by the DFG Emmy Noether program, the Hertie Foundation, and the Schram Foundation.

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Authors and Affiliations

  1. Vertebrate Gene Expression and Organ Function, Department of Molecular Biology, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany

    Alfred Nordheim

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  1. Alfred Nordheim
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  2. Bernd Knöll
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Correspondence to Alfred Nordheim .

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  1. , Department of Pathology and Laboratory M, The Children's Hospital of Philadelphia, Civic Center Boulevard 3501, Philadelphia, 19104, Pennsylvania, USA

    Thomas Curran

  2. Fondation IPSEN, Quai Georges Gorse 65, Boulogne-Billancourt Cedex, 92650, France

    Yves Christen

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Nordheim, A., Knöll, B. (2011). Actin-SRF Signaling in the Developing and Mature Murine Brain. In: Curran, T., Christen, Y. (eds) Two Faces of Evil: Cancer and Neurodegeneration. Research and Perspectives in Alzheimer's Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16602-0_3

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