Professor Elizabeth Smythe
Professor of Molecular Cell Biology
Room: C09 Florey building
Brief career history
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 cycle by rab5 and reversible phosphorylation. We are also interested in the interplay between endocytic trafficking and signaling pathways.
Functions of membrane microdomains on the endocytic pathway: integration of endocytosis and signalling
We are interested in the assembly and dynamics of membrane microdomains that are specialised for signalling on the endocytic pathway. Clathrin coated pits are microdomains responsible for the uptake of a wide variety of cargo. Using live-cell microscopy we are exploring how signalling cargo modulates clathrin coated pit dynamics via posttranslational modifications of the clathrin coat and how this impacts on downstream signalling.
The small GTPase, rab5, regulates many events on the early endocytic pathway including cargo selection, vesicle uncoating, endosomal fusion, and signalling. Guanine nucleotide exchange factors (GEFs) convert rab5 to its active GTP-bound ‘on’ state and they are also proposed to drive the spatial and temporal assembly of rab5 functional domains. We are using a variety of biochemical and morphological approaches to explore the function of Rme-6, a GEF that acts early in the endocytic pathway to integrate trafficking and signalling.
During embryonic development a surprisingly small number of signals are used repeatedly to form a whole organism. These same signals are also used in homeostasis. This means that cells need to respond to signals in a context specific manner. We are exploring how endocytosis contributes to context specific signalling using JAK/STAT signalling in Drosophila cells as a paradigm.
In addition to the molecular cell biology approaches discussed above we wish to understand how biophysical properties of membranes, in particular membrane tension, contributes to the regulation of microdomain formation. In the longer term our aim is to translate our findings into 3-D systems and ultimately whole organisms to understand the relationship between endocytosis and signalling.
Undergraduate and postgraduate taught modules
- Dang P, Smythe E & Furley AJW (2012) TAG1 regulates the endocytic trafficking and signaling of the semaphorin3A receptor complex.. J Neurosci, 32(30), 10370-10382. View this article in WRRO
- Ferreira F, Foley M, Cooke A, Cunningham M, Smith G, Woolley R, Henderson G, Kelly E, Mundell S & Smythe E (2012) Endocytosis of G protein-coupled receptors is regulated by clathrin light chain phosphorylation.. Curr Biol, 22(15), 1361-1370.
- Semerdjieva S, Shortt B, Maxwell E, Singh S, Fonarev P, Hansen J, Schiavo G, Grant BD & Smythe E (2008) Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6.. J Cell Biol, 183(3), 499-511. View this article in WRRO