Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells.
Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells.
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正常和转化的小脑细胞中转移1（MTSS1）的发育表达和分化相关的神经元特异性剪接。
DOI：
10.1186/1471-213x-7-111
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发表时间：
2007-10-09
影响因子：
--
通讯作者：
Schilling, Karl
中科院分区：
文献类型：
--
作者：
Glassmann, Alexander;Molly, Sabine;Surchev, Lachezar;Nazwar, Tommy A.;Holst, Martin;Hartmann, Wolfgang;Baader, Stephan L.;Oberdick, John;Pietsch, Torsten;Schilling, Karl
Mtss1编码一种肌动蛋白结合蛋白，在多种肿瘤中调节失调，与表皮细胞中的声波Hedgehog/Gli信号相互作用。鉴于该通路对于小脑发育和肿瘤发生的首要重要性，我们评估了mtss1在发育中的小脑和人髓母细胞瘤标本中的表达。在发育过程中，Mtss1在颗粒细胞中瞬时表达，从它们停止增殖到突触整合的时间点。颗粒细胞前体来源的髓母细胞瘤也表达它。在成人中枢神经系统中，Mtss1仅见于小脑浦肯野细胞。神经元分化伴随着Mtss1剪接的开关。虽然未成熟的颗粒细胞表达Mtss1变异体，在外周组织中也观察到，并包括外显子12，但在较成熟的颗粒细胞和成年浦肯野细胞中，该外显子被CNS特异的外显子12a所取代。对Mtss1的生物信息学分析表明，不同外显子的使用可能会影响与Fyn和Src的相互作用，这两个酪氨酸激酶以前被认为是小脑细胞迁移和组织发生的关键。此外，这种方法导致了两个进化保守的核定位序列的识别。它们与Mtss1的肌动蛋白细丝结合位点重叠，其中一个还含有潜在的PKA和PKC磷酸化位点。Mtss1的表达模式和剪接方式在小鼠小脑中都受到发育调节。对这些发现进行了讨论，以期探讨Mtss1在发育和成熟的小脑神经元中对细胞骨架动力学的潜在作用。
Mtss1 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 Mtss1 in the developing murine cerebellum and human medulloblastoma specimens. During development, Mtss1 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, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 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 Mtss1 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 Mtss1, and one also harbors a potential PKA and PKC phosphorylation site. Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons.