For a long time, protein transport into the extracellular space was believed to strictly depend on signal peptide-mediated translocation into the lumen of the endoplasmic reticulum. More recently, this view has been challenged and several groups have reported the secretion of several cytosolic proteins lacking signal peptides by unconventional transport pathways, which include: direct transport across the plasma membrane (PM); or a role for extracellular vesicles (EVs) and/or secretion via lysosomes. Our long-term goal is to fully understand the mechanism(s) of this unconventional protein transport.
Our strategy turns around two axes (Figure 1):
- firstly a hypothesis-driven approach consisting of testing and revisiting different models previously proposed in the literature.
- secondly a data-driven approach identifying new regulators of this unconventional protein transport using genome-scale functional screens based on CRISPR/Cas9 technology.
Both approaches, iteratively feeding on each other, should significantly enhance our understanding of what is currently a set of intriguing observations in an unbiased way and should lead to the characterisation of a new form of protein transport mechanism.
If you are interested in post-doc and PhD positions, please contact Kevin to discuss projects and opportunities to join the lab.
The Moreau Lab shows an unpredicted protein localisation on the surface of extracellular vesicles in the 1st issue of a new journal called Science Matters.
Sarah Stewart, Florian Gessler, Stefano Pluchino, Kevin Moreau. (2016). Inside-out: unpredicted Annexin A2 localisationon the surface of extracellular vesicles. Science Matters https://www.sciencematters.io/articles/201602000015
Moreau K, Ghislat G, Hochfeld W, Renna M, Zavadszky E, Runwal G, Puri C, Lee S, Siddiqi F, Menzies F, Ravikumar B, Rubinsztein D. Transcriptional regulation of Annexin A2 promotes starvation-induced autophagy. Nature Communications. 2015. Aug 20;6:8045. PMID: 26289944. PMCID: PMC4560779
Moreau K*, Fleming A*, Imarisio S, Lopez Ramirez A, Mercer JL, Jimenez-Sanchez M, Bento CF, Puri C, Zavodszky E, Siddiqi F, Lavau CP, Betton M, O’Kane CJ, Wechsler DS, Rubinsztein DC. PICALM modulates autophagy activity and tau accumulation. Nature Communications, 2014. Sep 22;5:4998. PMID: 25241929. PMCID: PMC4199285
Puri C, Renna M, Bento C, Moreau K, Rubinsztein D. Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell. 2013. Sep 12;154(6):1285-99.
Moreau K*, Ravikumar B*, Puri C, Rubinsztein D. Arf6 promotes autophagosome formation via effects on phosphatidylinositol 4,5-bisphosphate and phospholipase D. Journal of Cell Biology. 2012 Feb 20;196(4):483-96.
Moreau K, Ravikumar B, Renna M, Puri C, Rubinsztein D. Autophagosome precursor maturation requires homotypic fusion. Cell. 2011 Jul 22;146(2):303-17.
Ravikumar B*, Moreau K*, Jahreiss L, Puri C, Rubinsztein D. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nature Cell Biology. 2010 Aug;12(8):747-57
* Joint first authors