Regulation of Endocytic Recycling by FGD4, A CDC42 GEF
Cardenas, Jessica A.
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The family of Receptor Tyrosine Kinases (RTKs) are a group of cell surface receptors with the capability of activating, through phosphorylation, multiple kinase cascades in response to activation by an extracellular ligand. This allows a cell to respond to its environment and induce a range of cellular processes such as proliferation, differentiation, migration, and apoptosis. Unsurprisingly, these powerful transducers of extracellular signaling are often found mutated in human disease, such as cancer. Therefore, learning how these receptors are downregulated and processed once they have been activated may provide novel avenues of therapeutic intervention. How receptors are processed after internalization and fusion into the sorting endosome (also known as the early endosome) still largely remains unknown. Here, we discovered a Cdc42 GEF, FGD4, that may be important for shuttling ErbB receptors to the recycling endosome via a microtubule dependent mechanism. Through protein depletion studies we show that FGD4 is important for mitosis, microtubule stability, migration and endocytic trafficking of EGF, an ErbB1 ligand. Dynamic microtubule regulation are critical in these cell biological process, therefore we hypothesize that FGD4 may be regulating these diverse cell functions via a microtubule dependent mechanism. [Keywords: FGD4, Cdc42, endocytic recycling, microtubules, ErbB receptors]