AFAP120 regulates actin organization during neuronal differentiation.

AFAP120 regulates actin organization during neuronal differentiation.
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DOI:
10.1016/j.diff.2008.09.006
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发表时间:
2009-01
期刊:
影响因子:
2.9
通讯作者:
Lanier, Lorene M.
Lanier, Lorene M.
中科院分区:
生物学3区
文献类型:
--
作者:
Xu, Xiaohua;Harder, Jennifer;Flynn, Daniel C.;Lanier, Lorene M.

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在发育过程中,肌动蛋白细胞骨架的动态变化决定了细胞的运动和形态分化。在大多数成熟组织中,细胞通常具有最低限度的运动性,并且具有与其功能专门的形态。在转移性癌症中,细胞通常会失去其特定的形态并变得具有运动性。因此,调节运动状态和形态分化状态之间转变的蛋白质在决定癌症结局中发挥重要作用。AFAP120是一种神经元特异性蛋白,结合Src激酶和蛋白激酶C (PKC)并交联肌动蛋白丝。在这里,我们报道了AFAP120的表达和酪氨酸磷酸化在小脑中受到发育调节。在小脑培养中,PKC激活诱导了Src激酶依赖性的AFAP120磷酸化,表明AFAP120可能是Src的下游效应物。在PKC激活剂诱导分化的神经母细胞瘤细胞中,AFAP120的酪氨酸磷酸化似乎调节板层肌动蛋白结构的形成和随后的神经突起始。综上所述,这些结果表明AFAP120在神经元分化过程中组织动态肌动蛋白结构中发挥作用,并提示AFAP120可能有助于调节从运动前体到形态分化神经元的转变。
During development, dynamic changes in the actin cytoskeleton determine both cell motility and morphological differentiation. In most mature tissues, cells are generally minimally motile and have morphologies specialized to their functions. In metastatic cancer, cells generally loose their specialized morphology and become motile. Therefore, proteins that regulate the transition between the motile and morphologically differentiated states can play important roles in determining cancer outcomes. AFAP120 is a neuronal specific protein that binds Src Kinase and Protein Kinase C (PKC) and cross-links actin filaments. Here we report that expression and tyrosine phosphorylation of AFAP120 are developmentally regulated in the cerebellum. In cerebellar cultures, PKC activation induces Src-kinase dependent phosphorylation of AFAP120, indicating that AFAP120 may be a downstream effector of Src. In neuroblastoma cells induced to differentiate by treatment with a PKC activator, tyrosine phosphorylation of AFAP120 appears to regulate the formation of the lamellar actin structures and subsequent neurite initiation. Together, these results indicate that AFAP120 plays a role in organizing dynamic actin structures during neuronal differentiation and suggest that AFAP120 may help regulate the transition from motile precursor to morphologically differentiated neurons.
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