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Dr James Edgar

Dr James Edgar

Research Group Leader

Division of Immunology

Exosomes

Endosomes

Membrane traffic

Antigen presentation

Department of Pathology
University of Cambridge
Tennis Court Road
CB2 1QP

Research Interests

Our group focuses on the roles that endosomes and exosomes play in health and disease.

Endosomes are intracellular membrane-bound organelles that have several important roles. Endosomes regulate the trafficking of proteins and lipids between several pathways including the endocytic, secretory, recycling and degradative. As endosomes mature, proteins on the limiting membrane of endosomes can be sorted into domains that tubulate or vesiculate towards the cytosol for recycling. Conversely, proteins can be sorted to domains that subsequently invaginate inwards, away from the cytosol, where they form intralumenal vesicles (ILVs). Once an endosome has acquired ILVs, it becomes termed a late endosome, or multivesicular body (MVB). Trafficking a protein to an ILV has several functions; firstly it removes any signalling capacity of these proteins from interactions with the cytosol (this is especially important for downregulation of activated growth factor receptors), and secondly it packages proteins into vesicles that can be degraded or expelled from the cell.

MVBs have several potential fates. Fusion of an MVB with a lysosome forms a hybrid organelle, an endolysosome, where ILVs and their contents are degraded and recycled. Another fate of MVBs is that they may fuse with the plasma membrane where their ILVs are released into the extracellular milieu - these ILVs now become termed 'exosomes'.

Edgar-MVBs 

Exosomes are suggested to be involved in intercellular (between different cells) communication and have been implicated in a number of physiological and pathological processes, including antigen presentation, cancer and neurodegeneration. However, the basic cell biology which underlies their biology is relatively poorly understood.

Our lab aims to identify the molecular machinery which governs the behaviour of endosomes and exosomes. MHC-II becomes loaded with peptide in endosomes, and MHC-II is trafficked to ILVs - yet the biological rationale of doing this is not fully understood. We wish to understand what role MVBs play in MHC-II loading and ultimately how they contribute to deliver MHC-II-peptide complexes to the surface of cells.

We have recently shown that in mammalian cells exosomes can be tethered to the plasma membrane of cells following their release. This tethering is dependent upon a protein called tetherin, which plays a similar role in the retention of a number of virions. This highlights the possibility that exosomes have roles in short-range communication, in addition to longer-range communications. Our group will focus on understanding how and why exosomes are retained by this tethering process.

Research Supervision

Lab members:

Dr Panchali Kanvatirth (post-doctoral research associate)

Miss Anna Germon (PhD student)

 

Keywords

  • Immunology
  • MHC

Key Publications

Tetherin is an exosomal tether.

Edgar JR, Manna PT, Nishimura S, Banting G, Robinson MS.

Elife. 2016 Sep 22;5. pii: e17180. doi: 10.7554/eLife.17180. 

 

Q&A: What are exosomes, exactly?

Edgar JR.

BMC Biol. 2016 Jun 13;14:46. doi: 10.1186/s12915-016-0268-z.

  

ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-β accumulation.

Edgar JR, Willén K, Gouras GK, Futter CE.

J Cell Sci. 2015 Jul 15;128(14):2520-8. doi: 10.1242/jcs.170233. Epub 2015 May 22.

 

Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles.

Edgar JR, Eden ER, Futter CE.

Traffic. 2014 Feb;15(2):197-211. doi: 10.1111/tra.12139. Epub 2014 Jan 8.

  

Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease.

Hirst J, Edgar JR, Esteves T, Darios F, Madeo M, Chang J, Roda RH, Dürr A, Anheim M, Gellera C, Li J, Züchner S, Mariotti C, Stevanin G, Blackstone C, Kruer MC, Robinson MS.

Hum Mol Genet. 2015 Sep 1;24(17):4984-96. doi: 10.1093/hmg/ddv220. Epub 2015 Jun 17.

 
For a complete list of publications, please click here