Select Publications
A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies
Baird, H.J.M., Shun-Shion, A.S., De Oliveira, E.M., Stalder, D., Liang, L., Eden, J., Chambers, J.E., Farooqi, I.S.*, Gershlick, D.C.*, Fazakerley, D.J*. (2024) Journal of Biological Chemistry
In this collaborative project between our group, the group of Daniel Fazakerly (IMS, Cambridge) and the group of Sadaf Farooqi (IMS, Cambridge) we explored the effects of mutations of the gene encoding the protein leptin. Leptin is a hormone made in fat cells, and mutations in it are causal for severe genetic obesity. We develop an assay to study its secretion from fat cells and look at patient mutations. We find several mutations that have an underlying cause of not being able to be secreted from fat cells.
The role of the AP-1 adaptor complex in outgoing and incoming membrane traffic
Robinson, M.S., Antrobus, R., Sanger, A., Davies, A.K., Gershlick, D.C. (2024) Journal of Cell Biology
In this project led by Scottie Robinson's lab (CIMR, Cambridge), we explore AP-1 trafficking. AP-1 is an adaptor for clathrin-coated vesicles which bud from the TGN and endosomes. It is easy to tell where it buds from as we can see it on membranes, the question is- where do these vesicles go to? It has been controversial over the year and here using a combination of advanced light microscopy, single vesicle kinetics assays, and proteomics we show that they traffic in a retrograde direction i.e. back to the Golgi apparatus.
Recruitment of PI4KIIIβ to the Golgi by ACBD3 is dependent on an upstream pathway of a SNARE complex and golgins
Stalder, D., Yakunin, I., Gershlick, D. C. (2023) Molecular Biology of the Cell
ACBD3 is a Golgi localised protein that recruits (among other things) PI4KIIIβ to the Golgi apparatus. But how does ACBD3 get localised to the Golgi? We demonstrate that there is a two step mechanism with a SNARE complex and a set of golgins that allows ACBD3 to go to the Golgi at the right time and place to make new Golgi membrane.
The exocyst complex is an essential component of the mammalian constitutive secretory pathway
Pereira, C., Stalder, D., Anderson, G. S. F., Shun-Shion, A. S., Houghton, J., Antrobus, R., Chapman, M. A., Fazakerley, D. J., & Gershlick, D. C. (2023) Journal of Cell Biology
Using kinetic trafficking assays, genetics, and secretomics, a study lead by Maria and Daniele in the lab demonstrates the role of the exocyst complex in the secretory pathway.
Direct trafficking pathways from the Golgi apparatus to the plasma membrane
Stalder, D., Gershlick, D. C. (2020) Seminars in Cell & Developmental Biology
The first review from our group. We have tried to highlight some of the work that has inspired us, and discuss the open questions that interest us.
Cargo Segregation in the Golgi Stack Precedes Export into Distinct Transport Carriers
Chen, Y.*, Gershlick, D. C.*, Park, S. Y.* & Bonifacino J.S. (2017) Journal of Cell Biology
We used RUSH technology to synchronise the transport of endolysosomal transmembrane proteins after they are synthesised in the ER. We noticed that one class of proteins go directly to the endosomes and another class go via the plasma membrane, and they segregate from each other in the Golgi apparatus.
Structural Mechanism for Cargo Recognition by the Retromer Complex
Lucas, M.*, Gershlick, D. C.*, Vidaurrazaga, A., Bonifacino J.S. & Hierro A. (2016) Cell
We solved the structure of the cargo binding portion of the retromer complex, with the cytosolic domain of the cargo DMT1.
TSSC1 is Novel Component of the Endosomal Retrieval Machinery
Gershlick, D. C., Schindler, C., Chen, Y., & Bonifacino J.S. (2016) Molecular Biology of the Cell
We discovered a new protein involved in retrograde transport from the endosomal system to the Golgi and to the endosomes. This protein TSSC1 (now renamed EIPR1) interacts with the GARP and EARP tethering complexes and is likley to be involved in complex assembly.
Golgi-Dependent Transport of Vacuolar Sorting Receptors Is Regulated by COPII, AP1, and AP4 Protein Complexes in Tobacco
Gershlick, D. C., De Marcos Lousa, C., Foresti, O., Lee, A. J., Pereira, E. A., daSilva, L. L. P., Bottanelli, F., & Denecke, J. (2014) The Plant Cell
We dissected the trafficking itinerary of the plant vacuolar sorting receptor VSR2 (a distant homolog of the mammalian CD-MPR and Sortillin). We demonstrated that VSR2 trafficking first to the Golgi in a COPII dependent way and then traffics to the endosomal system by interacting with specific adapter proteins through protein-protein interactions in the cytosolic tail.
Other contributions
Pereira, C., & Gershlick, D. C. (2024). "BEACH domain proteins in membrane trafficking and disease" The Journal of Cell Biology 223(12), e202410147–e202410147.
Nturubika, B. D., Guardia, C. M., Gershlick, D. C., Logan, J. M., Martini, C., Heatlie, J. K., Lazniewska, J., Moore, C., Lam, G. T., Li, K. L., Ung, B. S. Y., Brooks, R. D., Hickey, S. M., Bert, A. G., Gregory, P. A., Butler, L. M., O’Leary, J. J., Brooks, D. A., & Johnson, I. R. D. (2024). "Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression" British Journal of Cancer 131(8), 1263–1278.
Macarelli, V., Harding, E. C., Gershlick, D. C., & Merkle, F. T. (2024). "A short sequence targets transmembrane proteins to primary cilia" Cells 13(13), 1156.
Tan, J., Virtue, S., Norris, D. M., Conway, O. J., Yang, M., Bidault, G., Gribben, C., Lugtu, F., Kamzolas, I., Krycer, J. R., Mills, R. J., Liang, L., Pereira, C., Dale, M., Shun-Shion, A. S., Baird, H. J. M., Horscroft, J. A., Sowton, A. P., Ma, M., Carobbio, S., Petsalaki, E., Murray, A. J., Gershlick, D. C., Nathan, J. A., Hudson, J. E., Vallier, L., Fisher-Wellman, K. H., Frezza, C., Vidal-Puig, A., & Fazakerley, D. J. (2024). "Limited oxygen in standard cell culture alters metabolism and function of differentiated cells" The EMBO Journal 43(11), 2127–2165
Romano-Moreno, M., Rojas, A. L., Williamson, C. D., Gershlick, D. C. , Lucas, M., Isupov, M. N., Bonifacino, J. S., Machner, M. P. , & Hierro, A. (2017). "Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL" PNAS 114(52)
Gershlick, D. C.* & Lucas, M.* (2017). "Endosomal Trafficking: Retromer and Retriever Are Relatives in Recycling" Current Biology 27(22)
Bernabe-Rubio, M., Gershlick, D. C., & Alonso M. A. (2017). “Physical Removal of the Midbody Remnant from Polarised Epithelial Cells Using Take-Up by Suction Pressure (TUSP)” Bio-protocol
Chen, Y., Gershlick, D. C., & Lippincott-Schwartz, J. (2017). “Assaying protein localization using Bromophenol blue (BPB) quench-assisted TIRF microscopy” Current Protocols in Cell Biology
Bernabe-Rubio, M., Andrs, G., Casares-Arias, J., Fernndez-Barrera, J., Rangel, L., Reglero-Real, N., Gershlick, D. C., Fernndez, J. J., Milln, J., Correas, I., Miguez, D. G., & Alonso M. A. (2016). “Novel role for the midbody in primary ciliogenesis by polarized epithelial cells” Journal of Cell Biology 214(3)
Bonifacino, J. S., Gershlick, D. C., & Dell’Angelica, E. C. (2016). “Immunoprecipitation” Current Protocols in Cell Biology 71(7.2.1-7.2.24)
Hierro, A., Gershlick, D. C., Adriana, L. R., & Bonifacino, J. S. (2015). “Formation of Tubulovesicular Carriers from Endosomes and Their Fusion to the Trans-Golgi Network” International Review of Cell and Molecular Biology. Vol. 318
Farias, G. G., Gershlick, D. C., & Bonifacino, J. S., (2014). “Going Forward with Retromer” Developmental Cell 29 (1)
Gershlick, D. C., De Marcos Lousa, C., Farmer, L., Denecke, J. (2014). “Routes to and From the Plasma Membrane: Bulk Flow Versus Signal Mediated Endocytosis” Plant Signaling & Behavior 9(7)
De Marcos Lousa, C.*, Gershlick, D. C.*, & Denecke, J.* (2012). “Mechanisms and Concepts Paving the Way towards a Complete Transport Cycle of Plant Vacuolar Sorting Receptors” The Plant Cell 24(5)
Bottanelli, F., Gershlick, D. C., & Denecke, J. (2012). “Evidence for Sequential Action of Rab5 and Rab7 GTPases in Prevacuolar Organelle Partitioning” Traffic 13(2)
Foresti, O., Gershlick, D. C., Bottanelli, F., Hummel, E., Hawes, C., & Denecke, J. (2010). “A Recycling-defective Vacuolar Sorting Receptor Reveals an Intermediate Compartment Situated Between Prevacuoles and Vacuoles in Tobacco” The Plant Cell 22(12)
* denotes equal contribution