JSAP1의 허파 및 신경계 발생과정에서의 기능

초록

The JNK interacting protein, JSAP1, has been identified in in vitro studies as a scaffold protein for MAPK signaling pathways. JSAP1 interacts also with focal adhesion kinase (FAK), a signaling molecule that is activated during the process of cell adhesion to extracellular matrix. To investigate the physiological function of JSAP1 in vivo, we generated mice lacking JSAP1. The JSAP1 null mutation produced severe defects in the morphogenetic differentiation of airways and alveoli during lung development, which led to the respiratory failure shortly after birth. The JSAP1 null mutation also produced various developing deficits in the brain, including an axon guidance defect of the corpus callosum, in which phospho-FAK and phospho-JNK were distributed at reduced levels. The axon guidance defect of the corpus callosum and anterior commissure in the jsap1-/-brain is partially rescued by transgenic expression of JIP1. Embryonic fibroblasts obtained from jsap1-/- showed cell adhesion deficits and the delayed reorganization of FAK during cell spreading. Together these results suggest that JSAP1 is essential for organizing cellular signals controlling cell adhesion, and the loss of JSAP1 leads to the impairments in the morphogenetic differentiation of lung and the axon guidance in developing brain.