| Research Abstract |
Clathrin-coated vesicles are involved in protein traffic from the trans-Golgi network (TGN) to lysosomes and in endocytosis of plasma membrane receptors. Recruitment of clathrin onto TGN and plasma membranes is mediated by adaptor protein (AP) complexes. The AP-1 and AP-2 complexes are involved in the formation of clathrin-coated vesicles from the TGN and plasma membrane, respectively. These AP complexes are composed of two large, one medium, and one small subunits. Recently, novel adaptor complexes, AP-3 and AP-4, have been identified and shown to function in the TGN and endosomes. Furthermore, We have recently identified a novel family of adaptor-like proteins, GGA1-GGA3, whose C-terminal ear domains are homologous to that of the, AP-1 γ-adaptin subunit, and shown that they function in the TGN. In this study, we have shown the followings on these adaptor proteins.
a) We have shown that the C-terminal ear domains of γ-adaptin and GGAs bind toγ-synergin and rabaptin-5, which function in the TGN and endosomes. Furthermore, we have revealed the X-ray crystal structures of the γ-adaptin ear domain and shown the molecular basis of its interaction with γ-synergin and rabaptin-5.
b) We have shown that the N-terminal VMS domain of GGAs binds to acidic cluster-dileucine (ACLL) motifs within the cytoplasmic domains of mannose 6-phosphate receptors and sortilin. Furthermore, we have revealed the X-ray crystal structure of the complex between the VHS domain and the ACLL peptide.
c) We have revealed the interaction modes among the AP subunits using the yeast three-hybrid system.
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