Amyloid precursor-like protein 2 increases the endocytosis, instability, and turnover of the H2-K(d) MHC class I molecule.
The defense against the invasion of viruses and tumors relies on the presentation of viral and tumor-derived peptides to CTL by cell surface MHC class I molecules. Previously, we showed that the ubiquitously expressed protein amyloid precursor-like protein 2 (APLP2) associates with the folded form of the MHC class I molecule K(d). In the current study, APLP2 was found to associate with folded K(d) molecules following their endocytosis and to increase the amount of endocytosed K(d). In addition, increased expression of APLP2 was shown to decrease K(d) surface expression and thermostability. Correspondingly, K(d) thermostability and surface expression were increased by down-regulation of APLP2 expression. Overall, these data suggest that APLP2 modulates the stability and endocytosis of K(d) molecules.
Tuli
Amit
A
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sharma
Mahak
M
McIlhaney
Mary M
MM
Talmadge
James E
JE
Naslavsky
Naava
N
Caplan
Steve
S
Solheim
Joyce C
JC
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D013696:Temperature
C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D006183:H-2 Antigens; D009419:Nerve Tissue Proteins