| Summary: | Lfc is a guanine nucleotide exchange factor (GEF) for RhoA and is negatively regulated by its association with the microtubule array. Tctex-1, a light chain subunit of the dynein motor complex, was identified as an Lfc-interacting protein in a yeast two-hybrid screen. In mouse embryonic fibroblast (MEF) cells, over-expression of Tctex-1 represses Lfc-induced actin stress fiber and focal adhesion complex formation. Here, we present biochemical evidence obtained from a real-time, nuclear magnetic resonance (NMR)-based assay indicating that the microtubule exerts its inhibitory effect on Lfc through a mechanism that is dependent on the presence of Tctex-1. We also present NMR structure data showing that Lfc and the dynein intermediate chain (DIC) bind to different surfaces of Tctex-1. The biochemical and structural data together support a model in which Lfc is recruited to the microtubules through the dynein cargo adaptor function of Tctex-1, resulting in inhibition of Lfc function.
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