Speaker
Dr
Norwood Suzanne
(University of Queensland)
Description
Retromer is a protein complex that plays a central role in endosomal traffficking. Recently, retromer dysfunction has been linked to several neurological disorders including Alzheimer’s and Parkinson’s diseases. The classical mammalian retromer complex consists of a heterotrimeric cargo recognition sub-complex (VPS26, VPS29 and VPS35) associated with a dimer of proteins from the SNX–BAR sorting nexin family that drives membrane deformation and tubulation. By recruiting the cargo-selective sub- complex to the forming tubules, the SNX–BAR coat complex mediates the retrograde transport of proteins from endosomes to the trans-Golgi network. Recent studies, however, have highlighted the functional diversity of retromer and identification of new interacting proteins has revealed that the role of retromer extends to aspects of endosome-to-plasma membrane sorting and regulation of signalling events. Emerging evidence indicates that cargo specificity is mediated by specific sorting nexins. These include SNX3, involved in the trafficking of the Wntless/MIG-14 protein, and SNX27, a PX-FERM protein that mediates the retrieval of the β2-adrenergic receptor. We have acquired crystallographic and small angle scattering data to determine how the core cargo recognition sub-complex assembles and to characterise the retromer-associated sorting nexins. We are using this structural information in combination with biochemical and biological studies in a synergistic approach to understand retromer-mediated endosomal protein sorting. The retromer complex is conserved across all eukaryotes and we are also currently exploring the structure and function of these proteins in zebrafish and *Chaetomium thermophilum*.
| Keywords | retromer, sorting nexin, small angle scattering, x-ray crystallography |
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Primary author
Dr
Norwood Suzanne
(University of Queensland)
Co-authors
Dr
Anthony Duff
(ANSTO)
Dr
Brett Collins
(The University of Queensland)
Dr
Kathleen Wood
(ANSTO)
Dr
Natalya Leneva
(University of Queensland)
Dr
Nathan Cowieson
(Australian Synchrotron)
Dr
Rajesh Ghai
(UNSW)
