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Characterisation of the AP-3 adaptor-like complex 10.17863/CAM.15876 Peden, Andrew Alexander Clathrin coated vesicles were the first type of coated vesicle to be characterised. The coat consists of two components, clathrin and adaptor (or AP) complexes, the AP-1 complex is associated with the clathrin coated vesicles that bud from the TGN and the AP-2 complex is associated with the clathrin coated vesicles that bud from the plasma membrane. A new type of adaptor-like complex was discovered in our laboratory and was published in 1996. The complex has been shown to consist of two known proteins, beta3B and mu3B, and two unknown proteins of 160kD and 22kD. Unlike the conventional adaptor complexes this complex is not associated with clathrin. The aim of this thesis was to complete the characterisation of the adaptor-like complex and to establish its function. My studies have shown that, the adaptor-like complex consist of an alpha/gamma like subunit, delta, a beta subunit (beta3A/B), a mu subunit (mu3A/B) and a sigma subunit (sigma3A/B). We named the adaptor-like complex AP-3, by analogy with the AP-1 and AP-2 complexes. The AP-3 complex is localised to perinuclear and more peripheral membranes in non-neuronal cells, with little overlap with endocytic markers. The beta subunit of the AP-3 complex is the major target for phosphorylation. Analysis of mice with mutations in the beta3A subunit, and in the delta subunit of the AP-3 complex, have revealed that the beta subunit is required for the stability of the mu subunit and that the delta subunit is essential for the stability of the whole complex. Further analysis of the mutant mice indicated that the mice lack significant levels of functional AP-3 complex. Studies on fibroblasts generated from these mice revealed that the AP-3 complex plays a role in the trafficking of LAMPI to lysosomes. University of Cambridge 2000-02-15 Thesis Doctoral Doctor of Philosophy (PhD) eng http://www.dspace.cam.ac.uk/handle/1810/243433 https://www.repository.cam.ac.uk/handle/1810/243433 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d1092378-2aff-4f36-9d98-a3ceb9965e18/download 053d0a620d129ac0e81a2a4930d7a43e https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/05cbbe3f-655a-46a4-aa93-805df1f2ad62/download 48dcdf38f646da27e5e4bc6c1893d4fc http://creativecommons.org/licenses/by/2.0/uk/ AP-3 Clathrin Membrane transport Trafficking Adaptor complex delta subunit beta3A subunit