| Summary: | 碩士 === 臺灣大學 === 分子與細胞生物學研究所 === 95 === Cas (p130Cas, Crk-associated substrate) is a tyrosine-phosphorylated 130 kilodalton docking protein that is required for the regulation of actin cytoskeleton organization and cell migration in mammalian fibroblasts. However, the role of p130cas during development is poorly understood. To investigate the function of p130cas during development, I have identified the single Drosophila ortholog of mammalian Cas family.
In situ hybridization and enhancer trap techniques revealed that p130cas is concentrated in the ventral nerve cord during embryogenesis and is enriched in the brain in third instar larvae. I have therefore generated several p130cas RNA interference (RNAi) transgenic lines to determine the possible function of p130cas during neurogenesis. Knockdown of p130cas expression in developing neurons resulted in partial fusion in the commissures axon fascicles of CNS, photoreceptor (R cell) axon targeting and guidance defects, and bulged synapse boutons at the neuromuscular junction. Moreover, reduced expression of p130cas in sensory organ precursor cells and proneural clusters resulted in bristle development defects. These phenotypes are similar to those of several effector mutants of Rho GTPase and mutants of regulatory proteins of Wasp/Wave complex. Taken together, these results suggest that the major functional roles of p130cas in Drosophila might be involved in the regulation of cytoskeleton reorganization via a Rho GTPase signaling pathway, and therefore affecting the appropriate neuron wiring and targeting.
Furthermore, I also found that reduced expression of p130cas in the developing wing often resulted in abnormal wing vein formation and blistered wings. These phenotypes are similar to mutants involved in focal adhesion formation. In summary, my results suggest that p130cas is likely to interact with multiple targets in a variety of developing processes by virtue of its modular protein binding domains.
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