Fitzgerald K, Greenwald I
Dept. of Biochemistry and Molecular Biophysics, Columbia University College Physicians and Surgeons, New York, NY 10032, USA.
Development. 1995 Dec;121(12):4275-82. doi: 10.1242/dev.121.12.4275.
Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1, influence different cell fate decisions during development. Here we show that APX-1 can fully substitute for LAG-2 when expressed under the control of lag-2 regulatory sequences. In addition, we demonstrate that truncated forms lacking the transmembrane and intracellular domains of both LAG-2 and APX-1 can also substitute for endogenous lag-2 activity. Moreover, we provide evidence that these truncated forms are secreted and able to activate LIN-12 and GLP-1 ectopically. Finally, we show that expression of a secreted DSL domain alone may enhance endogenous LAG-2 signalling. Our data suggest ways that activated forms of DSL ligands in other systems may be created.
Delta/Serrate/lag-2(DSL)家族的配体及其受体(lin-12/Notch家族成员)介导细胞间相互作用,这种相互作用决定了无脊椎动物和脊椎动物的细胞命运。在秀丽隐杆线虫中,两个DSL基因lag-2和apx-1在发育过程中影响不同的细胞命运决定。在此我们表明,当在lag-2调控序列的控制下表达时,APX-1可以完全替代LAG-2。此外,我们证明,缺失LAG-2和APX-1跨膜及胞内结构域的截短形式也能够替代内源性lag-2活性。而且,我们提供证据表明这些截短形式是可分泌的,并且能够异位激活LIN-12和GLP-1。最后,我们表明单独分泌的DSL结构域的表达可能增强内源性LAG-2信号传导。我们的数据提示了在其他系统中可能产生DSL配体激活形式的方式。