Abstract
Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia.
Highlights
IntroductionIt has been assumed that there are four, and only four, adaptor protein (AP) complexes
For many years, it has been assumed that there are four, and only four, adaptor protein (AP) complexes
Adaptor protein (AP) complexes facilitate the trafficking of cargo from one membrane compartment of the cell to another by recruiting other proteins to particular types of vesicles
Summary
It has been assumed that there are four, and only four, adaptor protein (AP) complexes. The first two AP complexes to be identified, AP-1 and AP-2, sort cargo proteins into clathrin-coated vesicles (CCVs). Both AP-1 and AP-2 are heterotetramers, consisting of two large subunits, sometimes called adaptins (c and b1 in AP-1; a and b2 in AP-2); a medium-sized subunit (m1 or m2); and a small subunit (s1 or s2) (Figure 1a and b). The AP-3 and AP-4 complexes were discovered by searching databases for homologues of the AP-1 and AP-2 subunits. AP-3 and AP-4 are heterotetramers, made up of d, b3, m3, and s3 subunits, and of e, b4, m4, and s4 subunits, respectively. Unlike AP-1 and AP-2, they appear to be able to work without clathrin (reviewed in [1,2])
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