| Project/Area Number |
10215201
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (B)
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Kyoto University (2001)
University of Tsukuba (1998-2000) |
|---|
Principal Investigator |
NAKAYAMA Kazuhisa Kyoto Univ., Grad. Sch. Pharmaceut. Sci., Professor, 薬学研究科, 教授 (40192679)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OHNO Hiroshi Kanazawa Univ., Cancer Res. Inst., Professor, がん研究所, 教授 (50233226)
|
|---|
| Project Period (FY) |
1998 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥51,500,000 (Direct Cost: ¥51,500,000)
Fiscal Year 2001: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1998: ¥11,000,000 (Direct Cost: ¥11,000,000)
|
|---|
| Keywords | clathrin / adapter / GGA / ARF / vesicular transtport / rabaptin-5 / γ-synergin / mannose 6-phosphate receptor / GGAタンパク質 / チロシン・シグナル |
|---|
| 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.
|
