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Author(s): Glassmann A (Glassmann, Alexander); Molly S (Molly, Sabine); Surchev L (Surchev, Lachezar); Nazwar TA (Nazwar, Tommy A.); Holst M (Holst, Martin); Hartmann W (Hartmann, Wolfgang); Baader SL (Baader, Stephan L.); Oberdick J (Oberdick, John); Pietsch T (Pietsch, Torsten); Schilling K (Schilling, Karl)
Title: Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor I (Mtss I) in normal and transformed cerebellar cells
Source: BMC DEVELOPMENTAL BIOLOGY 7: Art. No. 111
Date: 2007 OCT 9
Document Type: Journal : Article
DOI: 10.1186/1471-213X-7-111
Language: English
Comment:
Address: Univ Bonn, Inst Anat, D-5300 Bonn, Germany.
Univ Bonn, Inst Neuropathol, D-5300 Bonn, Germany. Univ Jena, Inst Anat, Jena, Germany. Ohio State Univ, Dept Neurosci, Ctr Mol Neurobiol, Columbus, OH 43210 USA. Med Univ Sofia, Dept Anat Histol & Embryol, BG-1431 Sofia, Bulgaria. Reprint: Schilling, K, Univ Bonn, Inst Anat, D-5300 Bonn, Germany.
E-mail: alexander.glassmann@uni-bonn.de
molly@uni-bonn.de surchev@hotmail.com tnazwar@uni-bonn.de martin.holst@uni-bonn.de wolfgang.hartmann@uni-bonn.de Stephan.Baader@mti.uni-jena.de oberdick.1@osu.edu t.pietsch@uni-bonn.de karl.schilling@uni-bonn.de Author Keywords:
KeyWords Plus: HEDGEHOG-RESPONSIVE GENE; CENTRAL-NERVOUS-SYSTEM; STRUCTURAL BASIS;
DENDRITIC SPINES; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; SONIC
HEDGEHOG; MESSENGER-RNA; MIM-B; SIGNAL-TRANSDUCTION
Abstract: Background: MtssI encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of MtssI in the developing murine cerebellum and human medulloblastoma specimens. Results: During development, MtssI is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, MtssI is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in MtssI splicing. Whereas immature granule cells express a MtssI variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of MtssI suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of MtssI, and one also harbors a potential PKA and PKC phosphorylation site. Conclusion: Both the pattern of expression and splicing of MtssI is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of MtssI for cytoskeletal dynamics in developing and mature cerebellar neurons.
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