The endosomal network acts as a master co-ordinator of traffic from both endocytic and bio-synthetic pathways. A vast multitude of cargoes are sorted within this system destined for distinct intra- cellular locations. The targeted and efficient distribution of endosomal cargo is reliant upon interactions with protein containing sorting machineries. Sorting machineries have evolved modular domains that associate with defining composites and morphologies of endosomal membranes that assure for correct steady state localisation and therefore function. The Sorting Nexins (SNXs) are a family of proteins characterised by the presence of a phosphoinositide-binding motif, termed the SNX- PX domain. By virtue of this domain, SNXs associate with membranes of the endocytic network and from here co-ordinate control over endocytosis, endosomal sorting and endosomal signalling. Two sub-families of SNXs are conjugated to additional modular domains, which confer to them diverse functionalities. In this thesis I have examined and characterised the mechanistic details of how SNX8 and SNX15 co-ordinate distinct events in endosomal trafficking. SNX8 utilises co-incidence detection to localise to high-curvature, phosphoinositide-enriched sub-domains of maturing endosomes; from here SNX8 co-ordinates the production of cargo-enriched carriers that are spatially distinct from more other well characterised tubular exit sites. By recruiting additional sorting machineries, SNX8 carriers are able to undergo long-range transport events, culminating in recognition and ultimately fusion with a recipient compartment, the Golgi apparatus, to facilitate cargo delivery. SNX15 associates with recently. endocytosed carriers, throuqh a direct association with clathrin, and facilitates their directional movement away from the cell periphery into the endo-Iysosomal degradative pathway.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:555629 |
| Date | January 2011 |
| Creators | Danson, Christopher |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0017 seconds