Re-routing of the invariant chain to the direct sorting pathway by introduction of an AP3-binding motif from LIMP II.
AP3 is a heteromeric adaptor protein complex involved in the biogenesis of late endosomal/lysosomal structures. It recognizes tyrosine- and leucine-based sorting signals present in the cytoplasmic tails or loops of a number of proteins and is thought to be responsible for the direct transport of these proteins from the Golgi network to late endosomal/lysosomal structures. We have previously reported (Rodionov, Höning, Silye, Kongsvik, von Figura, Bakke, 2002. Structural requirements for interactions between leucine-sorting signals and clathrin-associated adaptor protein complex AP3. J. Biol. Chem. 277, 47436-47443) that in vitro binding of AP3 to the leucine signals is dependent on the nature of three residues immediately upstream of the leucine signal and suggested that these three amino acids define whether the protein is sorted to endosomes via the plasma membrane (PM) or traffics directly to the late endosomes/lysosomes. In this paper, we show in vivo evidence that residues favoring AP3 binding introduced into a protein that is transported via the PM such as the invariant chain can re-route such protein into direct sorting to late endosomal/lysosomal structures.
Gupta
Shailly N
SN
Department of Molecular Biosciences, University of Oslo, N-0316 Oslo, Norway.
Kloster
Martine M
MM
Rodionov
Dmitrii G
DG
Bakke
Oddmund
O
D033963:Adaptor Protein Complex 3 / Q000737:chemistry*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D051116:Receptors, Scavenger / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D033963:Adaptor Protein Complex 3; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D051116:Receptors, Scavenger; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; C074299:SCARB2 protein, human; C045084:invariant chain