A conserved interaction between β1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C-elegans
A conserved interaction between β1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C-elegans
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DOI：
10.1016/s0960-9822(02)00764-9
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发表时间：
2002-04-16
期刊：
影响因子：
9.2
通讯作者：
Labouesse, EG
中科院分区：
文献类型：
--
作者：
Poinat, P;De Arcangelis, A;Labouesse, EG
背景：整合素是细胞外基质（ECM）配体的异二聚体（α）跨膜受体。通过与细胞连接处的分子伴侣相互作用，它们提供ECM和细胞骨架之间的连接，并调节细胞行为的许多方面。一些整合素相关的分子已被确定，然而，在许多情况下，它们在动物中的功能和作用仍有待澄清。结果：我们已经确定了NCK相互作用激酶（NIK），STE 20/germinal中心激酶（GCK）家族的成员，作为β 1A整合素胞质结构域的合作伙伴。我们发现NIK在小鼠胚胎的神经系统和其他组织中表达，并与转染细胞的细胞突起中的肌动蛋白和β 1整合素共定位。为了证明这种相互作用的功能意义，我们使用秀丽隐杆线虫，因为它只有一个β（PAT-3）整联蛋白链，两个α（INA-1和PAT-2）整联蛋白链，和一个非常保守的NIK直系同源物（NIK-15）。使用三种方法，我们表明，降低米格-15活性的结果过早分支的连合。当mig-15活性在弱的ina-1背景下受损时，观察到该缺陷的显著加重。针对mig-15或pat-3的神经元特异性RNA干扰导致类似的轴突缺陷，从而表明mig-15和pat-3在神经元中自主地作用于细胞。最后，我们展示了mig-15、ina-1和编码Rac GTP酶的基因之间的遗传相互作用。使用几种模型，我们提供了第一个证据，激酶NIK和整合素在体外和体内相互作用。这种相互作用是C.优雅
Background: Integrins are heterodimeric (alphabeta) transmembrane receptors for extracellular matrix (ECM) ligands. Through interactions with molecular partners at cell junctions, they provide a connection between the ECM and the cytoskeleton and regulate many aspects of cell behavior. A number of integrin-associated molecules have been identified; however, in many cases, their function and role in the animal remain to be clarified.Results: We have identified the Nck-interacting kinase (NIK), a member of the STE20/germinal center kinase (GCK) family, as a partner for the beta1A integrin cytoplasmic domain. We find that NIK is expressed in the nervous system and other tissues in mouse embryos and colocalizes with actin and beta1 integrin in cellular protrusions in transfected cells. To demonstrate the functional significance of this interaction, we used Caenorhabditis elegans, since it has only one beta (PAT-3) integrin chain, two alpha (INA-1 and PAT-2) integrin chains, and a well-conserved NIK ortholog (MIG-15). Using three methods, we show that reducing mig-15 activity results in premature branching of commissures. A significant aggravation of this defect is observed when mig-15 activity is compromised in a weak ina-1 background. Neuronal-specific RNA interference against mig-15 or pat-3 leads to similar axonal defects, thus showing that both mig-15 and pat-3 act cell autonomously in neurons. Finally, we show a genetic interaction between mig-15, ina-1, and genes that encode Rac GTPases.Conclusions. Using several models, we provide the first evidence that the kinase NIK and integrins interact in vitro and in vivo. This interaction is required for proper axonal navigation in C. elegans.