Phosphoinositide-mediated endosomal sorting and signaling
The
endocytic network comprises a series of interconnected tubulo-vesicular membranous
compartments that together regulate various sorting and signaling events.
While it is clear that defects in endocytic function underlies a variety of
human diseases (e.g. cancer, neurodegeneration, pathogenic infection), our
understanding of the molecular entities that regulate endosomal function remains
limited. Our research is examining a family of mammalian phosphoinositide-binding
proteins - the sorting nexins – that play fundamental roles in orchestrating
the formation of protein complexes involved in endosomal sorting and signaling.
e-mail: Pete.Cullen@bristol.ac.uk
Selected Publications
Steinberg F, Heesom KJ, Bass MD, Cullen PJ: Sorting nexin-17 protects integrins from degradation by sorting between lysosomal and recycling pathways. Journal of Cell Biology 197, 219-230 (2012). [In this Issue. Leslie M: Wait, save that integrin! Journal of Cell Biology 197, 162 (2012)].
Cullen PJ, Korswagen HC: Sorting nexins provide diversity for retromer-dependent trafficking events. Nature Cell Biology 14, 29-37 (2012).
Harterink M, Port F‡, Lorenowicz MJ‡, McGough IJ‡, Sikankova M, Betist MC, van Weering JRT, van Heesbeen RGHP, Middelkoop T, Basler K, Cullen PJ*, Korswagen HC*: A sorting nexin-3 dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion. Nature Cell Biology 13, 914-923 (2011). ‡joint 2nd authors. *joint senior/corresponding authors. [News and Views. Johannes L, Wunder C: The SNXy flavours of endosomal sorting. Nature Cell Biology 13, 884-886 (2011). Have you seen? Spang A: Signalling gets sorted by retromer. EMBO Journal 30, 2988-2989 (2011)]. [F1000 – must read].
Wassmer T, Attar N, Harterink M, van Weering JR, Traer CJ, Oakley J, Goud B, Stephens DJ, Verkade P, Korswagen HC, Cullen PJ: The retromer coat complex coordinates endosomal sorting and dynein-mediated transport with carrier recognition by the trans-Golgi network. Developmental Cell 17, 110-122 (2009).
Cullen PJ: Endosomal sorting and signalling: an emerging role for sorting nexins. Nature Reviews: Molecular Cell Biology 9, 574-582 (2008).
Traer CJ, Rutherford AC, Palmer KJ, Wassmer T, Oakley JD, Carlton JG, Kremerskothen J, Stephens DJ, Cullen PJ: Sorting nexin-4 co-ordinates endosomal sorting of transferrin receptor with dynein-mediated transport into the endocytic recycling compartment. Nature Cell Biology 9, 1370-1380 (2007).
Carlton JG, Bujny MV, Peter BJ, Oorschot VMJ, Rutherford AC, Mellor
H, Klumperman J, McMahon HT, Cullen PJ: Sorting nexin-1 mediates tubular endosome-to-TGN
transport through co-incidence sensing of high curvature membranes and 3-phosphoinositides.
Current Biology 14, 1791-1800 (2004). [Research Roundup. LeBrasseur N: SNX1 hugs the curves. Journal of Cell Biology 4, 581 (2004)].