Williams Michael J
Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen, UK.
BMC Immunol. 2009 Mar 25;10:17. doi: 10.1186/1471-2172-10-17.
When the parasitoid wasp Leptopilina boulardi lays its eggs in Drosophila larvae phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. This requires these circulating immunosurveillance cells (haemocytes) to change from a non-adhesive to an adhesive state enabling them to bind to the invader. Interestingly, attachment of leukocytes, platelets, and insect haemocytes requires the same adhesion complexes as epithelial and neuronal cells.
Here evidence is presented showing that the Drosophila L1-type cell adhesion molecule Neuroglian (Nrg) is required for haemocytes to encapsulate L. boulardi wasp eggs. The amino acid sequence FIGQY containing a conserved phosphorylated tyrosine is found in the intracellular domain of all L1-type cell adhesion molecules. This conserved tyrosine is phosphorylated at the cell periphery of plasmatocytes and lamellocytes prior to parasitisation, but dephosphorylated after immune activation. Intriguingly, another pool of Nrg located near the nucleus of plasmatocytes remains phosphorylated after parasitisation. In mammalian neuronal cells phosphorylated neurofascin, another L1-type cell adhesion molecule interacts with a nucleokinesis complex containing the microtubule binding protein lissencephaly-1 (Lis1) 1. Interestingly in plasmatocytes from Nrg mutants the nucleokinesis regulating protein Lissencephaly-1 (Lis1) fails to localise properly around the nucleus and is instead found diffuse throughout the cytoplasm and at unidentified perinuclear structures. After attaching to the wasp egg control plasmatocytes extend filopodia laterally from their cell periphery; as well as extending lateral filopodia plasmatocytes from Nrg mutants also extend many filopodia from their apical surface.
The Drosophila cellular adhesion molecule Neuroglian is expressed in haemocytes and its activity is required for the encapsulation of L. boularli eggs. At the cell periphery of haemocytes Neuroglian may be involved in cell-cell interactions, while at the cell centre Neuroglian regulates the localisation of the nucleokinesis complex protein lissencephaly-1.
当寄生蜂布氏丽蝇蛹集金小蜂在果蝇幼虫体内产卵时，称为浆血细胞的吞噬细胞和称为片层细胞的特化细胞会包裹这些卵。这需要这些循环免疫监视细胞（血细胞）从非黏附状态转变为黏附状态，使其能够与入侵者结合。有趣的是，白细胞、血小板和昆虫血细胞的附着需要与上皮细胞和神经元细胞相同的黏附复合物。
本文提供的证据表明，果蝇L1型细胞黏附分子神经胶质蛋白（Nrg）是血细胞包裹布氏丽蝇蛹集金小蜂卵所必需的。在所有L1型细胞黏附分子的胞内结构域中都发现了包含保守磷酸化酪氨酸的氨基酸序列FIGQY。这个保守的酪氨酸在寄生前在浆血细胞和片层细胞的细胞周边被磷酸化，但在免疫激活后去磷酸化。有趣的是，位于浆血细胞细胞核附近的另一组Nrg在寄生后仍保持磷酸化状态。在哺乳动物神经元细胞中，另一种L1型细胞黏附分子磷酸化神经束蛋白与包含微管结合蛋白无脑回蛋白-1（Lis1）的核运动复合物相互作用。有趣的是，在Nrg突变体的浆血细胞中，核运动调节蛋白无脑回蛋白-1（Lis1）未能在细胞核周围正确定位，而是在整个细胞质和未识别的核周结构中呈弥散分布。附着在黄蜂卵上后，对照浆血细胞从其细胞周边横向伸出丝状伪足；除了横向伸出丝状伪足外，Nrg突变体的浆血细胞还从其顶端表面伸出许多丝状伪足。
果蝇细胞黏附分子神经胶质蛋白在血细胞中表达，其活性是包裹布氏丽蝇蛹集金小蜂卵所必需的。在血细胞的细胞周边，神经胶质蛋白可能参与细胞间相互作用，而在细胞中心，神经胶质蛋白调节核运动复合物蛋白无脑回蛋白-1的定位。
