Membrane traffic

Surprisingly, the complex biogenesis of many signaling proteins, including those associated with human diseases, remains poorly understood. This, combined with the fact that approximately 60% of current drugs target membrane proteins, illustrates the importance to understand how membrane proteins are successfully made, integrated into the membrane and trafficked within the secretory pathway.

The Membrane Traffic lab is interested in several aspects of membrane protein homeostasis (‘Proteostasis’) including how membrane proteins are made, degraded or trafficked within the secretory pathway.

We use a combination of cellular biochemistry and mouse physiology in our experimental approaches, focusing particularly on models of inflammation and/or metabolic homeostasis.

Our work currently focuses on three areas being developed:

1. How membrane trafficking regulates signalling controlled by the metalloprotease ADAM17/TACE.
2. Role of quality control in the secretory pathway in vivo in mice, during development and disease.
3. Genetic screens to identify novel trafficking factors.

• Adrain, C., Zettl, M., Christova, Y., Taylor, N., Freeman, M. (2012)  Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. (joint-first author). Science  355 : 225-8
• Zettl, M., Adrain, C. , Strisovsky, K., Lastun, V., Freeman, M. (2011)  Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell   145 : 79-91
• Adrain, C., Strisovsky, K., Zettl, M., Hu, L., Lemberg, M.K., Freeman, M. (2011) Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep.   12 : 421-7
• Adrain, C. , Duriez, P.J., Brumatti, G., Delivani, P., Martin, S.J. (2006)  The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and perturbs microtubule polymerization dynamics J Biol Chem   281 : 8118-25
• Delivani, P., Adrain, C. , Taylor, R.C., Duriez, P.J., Martin, S.J. (2006)  Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics Mol Cell    21 : 761-73
• Adrain, C. , Murphy, B.M., Martin, S.J. (2005)  Molecular ordering of the caspase activation cascade initiated by the CTL/NK protease, Granzyme B J. Biol. Chem  280 : 4663-4673
• Adrain, C. , Creagh, E.M., Cullen, S.P., Martin, S.J. (2004)  Caspase-dependent inactivation of proteasome function during programmed cell death in Drosophila and man (joint-first author) J. Biol. Chem   279 : 36923-36930
• Adrain, C., Creagh, E.M., Martin, S.J. (2001)  Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2.EMBO J.   20 : 6627-36