O'Keefe D D, Thor S, Thomas J B
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Development. 1998 Oct;125(19):3915-23. doi: 10.1242/dev.125.19.3915.
LIM domains are found in a variety of proteins, including cytoplasmic and nuclear LIM-only proteins, LIM-homeodomain (LIM-HD) transcription factors and LIM-kinases. Although the ability of LIM domains to interact with other proteins has been clearly established in vitro and in cultured cells, their in vivo function is unknown. Here we use Drosophila to test the roles of the LIM domains of the LIM-HD family member Apterous (Ap) in wing and nervous system development. Using a rescuing assay of the ap mutant phenotype, we have found that the LIM domains are essential for Ap function. Furthermore, expression of LIM domains alone can act in a dominant-negative fashion to disrupt Ap function. The Ap LIM domains can be replaced by those of another family member to generate normal wing structure, but LIM domains are not interchangeable during axon pathfinding of the Ap neurons. This suggests that the Ap LIM domains mediate different protein interactions in different developmental processes, and that LIM domains can participate in conferring specificity of target gene selection.
LIM结构域存在于多种蛋白质中，包括仅含细胞质和细胞核LIM的蛋白质、LIM同源结构域（LIM-HD）转录因子和LIM激酶。尽管LIM结构域与其他蛋白质相互作用的能力已在体外和培养细胞中得到明确证实，但其在体内的功能尚不清楚。在这里，我们利用果蝇来测试LIM-HD家族成员无翅（Ap）的LIM结构域在翅膀和神经系统发育中的作用。通过对ap突变体表型的拯救试验，我们发现LIM结构域对Ap的功能至关重要。此外，单独表达LIM结构域可以以显性负性方式破坏Ap的功能。Ap的LIM结构域可以被另一个家族成员的结构域取代以产生正常的翅膀结构，但在Ap神经元的轴突导向过程中，LIM结构域是不可互换的。这表明Ap的LIM结构域在不同的发育过程中介导不同的蛋白质相互作用，并且LIM结构域可以参与赋予靶基因选择的特异性。
