The Fifth Adaptor Protein Complex

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.

Identification and Dynamics of Arabidopsis Adaptor Protein-2 Complex and Its Involvement in Floral Organ Development

“…AP-4 is involved in TGN-toendosome trafficking for specific cargo proteins, such as amyloid precursor protein (Burgos et al, 2010). The recently identified AP-5 complex is localized to late endosomes (Hirst et al, 2011). The Arabidopsis thaliana genome contains all five of the putative AP genes (Bassham et al, 2008;Hirst et al, 2011); however, our knowledge of their roles in membrane trafficking and physiological function is still limited.…”

“…The recently identified AP-5 complex is localized to late endosomes (Hirst et al, 2011). The Arabidopsis thaliana genome contains all five of the putative AP genes (Bassham et al, 2008;Hirst et al, 2011); however, our knowledge of their roles in membrane trafficking and physiological function is still limited. Arabidopsis AP-2 has the potential to interact with a vacuolar sorting receptor (Happel et al, 2004).…”

Arabidopsis μ-adaptin subunit AP1M of adaptor protein complex 1 mediates late secretory and vacuolar traffic and is required for growth

“…Occurrence of a fourth adaptor complex AP-4 (e/β4/μ4/σ4) has been described or inferred in only a few organisms such as humans, mice, and Arabidopsis and is known to be involved in basolateral sorting in epithelial cells (1,16). Very recently, an AP-5 complex has been found through a structure-prediction program and shown to be involved in clathrin-independent endosomal trafficking at the late endosome in mammals (17).…”

“…There might be an additional AP complex because Arabidopsis appears to have orthologs of several subunits of a recently identified mammalian AP-5 complex; however, no matching sigma subunit has been identified (17). So far, the AP-3 complex comprising the subunits δ, β3, muD and σ3 is the only one that has been functionally characterized in Arabidopsis.…”

“…It is not clear which of the medium adaptins muA or muB1/muB2 is a subunit of the secretory AP-1 complex or the endocytic AP-2 complex. By sequence similarity, muA and muB might be more closely related to mammalian μ2 and μ1 subunits, respectively (1,17). However, muA adaptin was localized to the trans-Golgi in Arabidopsis suspension cells and shown to interact with the cytosolic tail of pea vacuolar sorting receptor (VSR)1 and mammalian TGN38 in vitro (20).…”