Temporal and spatial regulation of the early endocytic pathway by rab5 and its GEF, hRME-6
Prof. Elizabeth Smythe University of Sheffield Seminar sponsored by GENEFLOW
Our lab is interested in the molecular mechanisms of cargo sorting along the endocytic pathway with particular emphasis on the regulation of the clathrin coated vesicle (CCV) cycle by rab5 and reversible phosphorylation. We are also interested in the interplay between endocytic trafficking and signaling pathways. Recent results from our lab have focused on the role of hRME-6, which is a guanine nucleotide exchange factor for rab5 that functions in clathrin coated vesicles. I will discuss our recent results on the role of rab5/hRME-6 in mediating disassembly of the AP2 adaptor complex from CCVs. AP2 assembly onto the plasma membrane during coated pit formation requires PtdIns(4,5)P2 and phosphorylation of the µ2 subunit of AP2. During AP2 uncoating, rab5/hRME-6 regulates PtdIns(4,5)P2 turnover and promotes µ2 dephosphorylation thus demonstrating a mechanistic symmetry to AP2 assembly during the disassembly process. In addition to its GEF domain, hRME-6 has a rasGAP domain, making it an excellent candidate to integrate trafficking and signaling pathways. Key publications: • Zhang, C.X., Engquist-Goldstein, A.E., Carreno, S., Owen, D.J., Smythe, E. and Drubin, D.G. (2005) Multiple roles for GAK in clathrin-mediated sorting events. Traffic 6: 1103-1113 • Jackson, A.P., Flett, A., Smythe, C., Hufton, L., Wettey, F.R. and Smythe, E. (2003) Clathrin regulates cargo recruitment in to clathrin coated pits by activation of the AP2 adaptor µ2 kinase. J Cell Biol. 2: 231-6. Semerdjieva et al. Co-ordinated regulation of AP2 uncoating from clathrin coated vesicles by rab5 and hRME-6 J Cell Biol In press Web site: http://www.shef.ac.uk/bms/research/esmythe
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