The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding.
We report that the Vps10p domain receptor sorLA binds the adaptor proteins GGA1 and -2, which take part in Golgi-endosome sorting. The GGAs bind with differential requirements via three critical residues in the C-terminal segment of the sorLA cytoplasmic tail. Unlike in sortilin and the mannose 6-phosphate receptors, the GGA-binding segment in sorLA contains neither an acidic cluster nor a dileucine. Our results support the concept of sorLA as a potential sorting receptor and suggest that key residues in sorLA and sortilin conform to a new type of motif (psi-psi-X-X-phi) defining minimum requirements for GGA binding to cytoplasmic receptor domains.
Jacobsen
Linda
L
Department of Molecular and Cellular Neurobiology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands. lija@bio.vu.nl
Madsen
Peder
P
Nielsen
Morten S
MS
Geraerts
Wijnand P M
WP
Gliemann
Jørgen
J
Smit
August B
AB
Petersen
Claus M
CM
D020727:ADP-Ribosylation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008715:Methionine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; D011506:Proteins; D011973:Receptors, LDL; D008715:Methionine; D020727:ADP-Ribosylation Factors