Professor Elizabeth Smythe

School of Biosciences

Professor of Cell Biology

Director, Centre for Membrane Interactions and Dynamics

e.smythe@sheffield.ac.uk
+44 114 222 4635

C09 Florey Building, Firth Court

Full contact details

Professor Elizabeth Smythe
School of Biosciences
C09 Florey Building
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

2002-present: Professor of Molecular Cell Biology, University of Sheffield
1992-2002: MRC Senior Fellow and Principal Investigator, Wellcome Trust BioCentre, University of Dundee
1989-1992: NATO/SERC postdoctoral fellow, The Scripps Research Institute, California
1986-1989: Postdoctoral research assistant, University of Dundee.
1986: PhD, Trinity College, Dublin
1982: B.A. (Mod), Trinity College, Dublin

Research interests

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.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

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

All publications

Journal articles

Smythe E (2022) Clathrin coated pits as signaling platforms for Akt signaling. Journal of Cell Biology, 221(4).
Naik S, Wood AR, Ongenaert M, Saidiyan P, Elstak ED, Lanz HL, Stallen J, Janssen R, Smythe E & Erdmann KS (2021) A 3d renal proximal tubule on chip model phenocopies lowe syndrome and dent ii disease tubulopathy. International Journal of Molecular Sciences, 22(10).
Moore R, Vogt K, Acosta-Martin A, Shire P, Zeidler M & Smythe E (2020) Integration of JAK/STAT receptor/ligand trafficking, signalling and gene expression in Drosophila melanogaster cells. Journal of Cell Science, 133.
King JS & Smythe E (2020) Water loss regulates cell and vesicle volume. Science, 367(6475), 246-247.
Maib H, Ferreira F, Vassilopoulos S & Smythe E (2018) Cargo regulates clathrin-coated pit invagination via clathrin light chain phosphorylation. The Journal of Cell Biology, 217(12), 4253-4266. View this article in WRRO
Moore R, Pujol MG, Zhu Z & Smythe E (2018) Interplay of Endocytosis and Growth Factor Receptor Signalling, 181-202.
Maib H, Smythe E & Ayscough KR (2017) Forty years on: clathrin-coated pits continue to fascinate. Molecular Biology of the Cell, 28(7), 843-847. View this article in WRRO
Smythe E (2015) Role of the Rab5 Guanine Nucleotide Exchange Factor, Rme-6, in the Regulation of Clathrin-Coated Vesicle Uncoating, 283-293.
Fürthauer M & Smythe E (2014) Systems dynamics in endocytosis. Traffic, 15(3), 338-346.
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.
Ferreira FJ, Foley M, Cooke A, Cunningham M, Henderson G, Kelly E, Mundell S & Smythe E (2012) Phosphorylation of clathrin light chain b regulates GPCR trafficking.. MOLECULAR BIOLOGY OF THE CELL, 23.
Wright VM, Vogt KL, Smythe E & Zeidler MP (2011) Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3.. Cell Signal, 23(5), 920-927.
Wright VM, Vogt KL, Smythe E & Zeidler MP (2011) Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cellular Signalling, 23(5), 920-927.
Montagnac G, de Forges H, Smythe E, Gueudry C, Romao M, Salamero J & Chavrier P (2011) Decoupling of Activation and Effector Binding Underlies ARF6 Priming of Fast Endocytic Recycling. Current Biology.
Montagnac G, De Forges H, Smythe E, Gueudry C, Romao M, Salamero J & Chavrier P (2011) Decoupling of activation and effector binding underlies ARF6 priming of fast endocytic recycling. Current Biology, 21(7), 574-579.
Vidal OM, Stec W, Bausek N, Smythe E & Zeidler MP (2010) Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. Development, 137(21), e2107-e2107.
Vidal OM, Stec W, Bausek N, Smythe E & Zeidler MP (2010) Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking.. J Cell Sci, 123(Pt 20), 3457-3466.
Robertson AS, Smythe E & Ayscough KR (2009) Functions of actin in endocytosis.. Cell Mol Life Sci, 66(13), 2049-2065.
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
Parker LC, Prestwich EC, Ward JR, Smythe E, Berry A, Triantafilou M, Triantafilou K & Sabroe I (2008) A phosphatidylserine species inhibits a range of TLR- but not IL-1beta-induced inflammatory responses by disruption of membrane microdomains.. J Immunol, 181(8), 5606-5617.
Smythe E & Ayscough KR (2006) Actin regulation in endocytosis.. J Cell Sci, 119(Pt 22), 4589-4598.
Zhang CX, Engqvist-Goldstein AEY, Carreno S, Owen DJ, Smythe E & Drubin DG (2005) Multiple roles for cyclin G-associated kinase in clathrin-mediated sorting events. TRAFFIC, 6(12), 1103-1113.
Osborne A, Flett A & Smythe E (2005) Endocytosis Assays in Intact and Permeabilized Cells. Current Protocols in Cell Biology, 27(1), 11.18.1-11.18.24.
Flett A, Semerdjieva S, Jackson AP & Smythe E (2005) Regulation of the clathrin-coated vesicle cycle by reversible phosphorylation.. Biochem Soc Symp(72), 65-70.
Smythe E (2004) Cell biology - Light on pits. NATURE, 431(7009), 641-642.
Jackson AP, Flett A, Smythe C, Hufton L, Wettey FR & Smythe E (2003) Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor micro2 kinase.. J Cell Biol, 163(2), 231-236. View this article in WRRO
Smythe E (2003) Clathrin-coated vesicle formation: a paradigm for coated-vesicle formation.. Biochem Soc Trans, 31(Pt 3), 736-739.
Smythe E & Ayscough KR (2003) The Ark1/Prk1 family of protein kinases. Regulators of endocytosis and the actin skeleton.. EMBO Rep, 4(3), 246-251.
Smythe E (2002) Regulating the clathrin-coated vesicle cycle by AP2 subunit phosphorylation.. Trends Cell Biol, 12(8), 352-354.
Smythe E (2002) Direct interactions between rab GTPases and cargo.. Mol Cell, 9(2), 205-206.
Hill E, Olusanya O, van der Kaay J, Downes CP, Andrews PD, Swedlow JR & Smythe E (2001) Regulation of clathrin-coated vesicle formation.. Biochem Soc Trans, 29(Pt 4), 375-377.
Olusanya O, Andrews PD, Swedlow JR & Smythe E (2001) Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo.. Curr Biol, 11(11), 896-900.
Smythe E, Olusanya O, Hill EV & Osborne A (2001) The regulation and mechanism of clathrin coated vesicle formation. Biochemical Society Transactions, 29(3), A45-A45.
Hill E, van Der Kaay J, Downes CP & Smythe E (2001) The role of dynamin and its binding partners in coated pit invagination and scission.. J Cell Biol, 152(2), 309-323. View this article in WRRO
Gagescu R, Gruenberg J & Smythe E (2000) Membrane dynamics in endocytosis: Structure-function relationship. Traffic, 1(1), 84-89.
McLauchlan H, Newell J, Morrice N, Osborne A, West M & Smythe E (1998) A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits.. Curr Biol, 8(1), 34-45.
Smythe E (1996) Endocytosis.. Subcell Biochem, 27, 51-92.
Smythe E, Smith PD, Jacob SM, Theobald J & Moss SE (1994) Endocytosis occurs independently of annexin VI in human A431 cells. Journal of Cell Biology, 124(3), 301-306. View this article in WRRO
Smythe E, Carter LL & Schmid SL (1992) Cytosol- and clathrin-dependent stimulation of endocytosis in vitro by purified adaptors. Journal of Cell Biology, 119(5), 1163-1171. View this article in WRRO
Smythe E, Pypaert M, Lucocq J & Warren G (1989) Formation of coated vesicles from coated pits in broken A431 cells.. J Cell Biol, 108(3), 843-853. View this article in WRRO
Warren G, Woodman P, Pypaert M & Smythe E (1988) Cell-free assays and the mechanism of receptor-mediated endocytosis. Trends in Biochemical Sciences, 13(12), 462-465.

Conference proceedings papers

Giralt-Pujol M & Smythe E (2017) 150 A high throughput sirna screening identifies rac1 as a potential modulator of the endocytosis of the tyrosine kinase receptor tie2. Heart, Vol. 103(Suppl 5) (pp A110-A110)
Brown S, Smythe E, Strutt D, Whitworth A & Zeidler M (2009) The University of Sheffield RNAi Screening facility: Genome-wide RNAi screens in Drosophila cells using a 2nd generation in silico optimized library. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S290-S290)

Grants

MRC
BHF
EU

Teaching activities

Undergraduate and postgraduate taught modules

Undergraduate:

BMS109 Cell & Molecular
BMS6082 Practical Cell Biology (Coordinator)
Level 3 Practical and Dissertation Modules

Masters (MSc):

BMS6082 Practical Cell Biology (Coordinator)

Professional activities and memberships

Member of:

the Faculty of 1000 (2001-)
the Editorial Board of the Biochemical Journal (2004-2007) Renewed (2007-2011)
the MRC College of Experts (2006-2010)
Executive Secretary of the British Society for Cell Biology (2006-2011)