Mechanism for amyloid precursor-like protein 2 enhancement of major histocompatibility complex class I molecule degradation

Amit Tuli, Mahak Sharma, Haley L. Capek, Naava Naslavsky, Steven H Caplan, Joyce C Solheim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Earlier studies have demonstrated interaction of the murine major histocompatibility complex (MHC) class I molecule Kd with amyloid precursor-like protein 2 (APLP2), a ubiquitously expressed member of the amyloid precursor protein family. Our current findings indicate that APLP2 is internalized in a clathrin-dependent manner, as shown by utilization of inhibitors of the clathrin pathway. Furthermore, we demonstrated that APLP2 and Kd bind at the cell surface and are internalized together. The APLP2 cytoplasmic tail contains two overlapping consensus motifs for binding to the adaptor protein-2 complex, and mutation of a tyrosine shared by both motifs severely impaired APLP2 internalization and ability to promote Kd endocytosis. Upon increased expression of wild type APLP2, Kd molecules were predominantly directed to the lysosomes rather than recycled to the plasma membrane. These findings suggest a model in which APLP2 binds Kd at the plasma membrane, facilitates uptake of Kd in a clathrin-dependent manner, and routes the endocytosed Kd to the lysosomal degradation pathway. Thus, APLP2 has a multistep trafficking function that influences the expression of major histocompatibility complex class I molecules at the plasma membrane.

Original languageEnglish (US)
Pages (from-to)34296-34307
Number of pages12
JournalJournal of Biological Chemistry
Volume284
Issue number49
DOIs
StatePublished - Dec 4 2009

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Amyloid beta-Protein Precursor
Major Histocompatibility Complex
Amyloid
Degradation
Molecules
Clathrin
Proteins
Cell membranes
Cell Membrane
Endocytosis
Adaptor Protein Complex 2
Lysosomes
Tyrosine
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mechanism for amyloid precursor-like protein 2 enhancement of major histocompatibility complex class I molecule degradation. / Tuli, Amit; Sharma, Mahak; Capek, Haley L.; Naslavsky, Naava; Caplan, Steven H; Solheim, Joyce C.

In: Journal of Biological Chemistry, Vol. 284, No. 49, 04.12.2009, p. 34296-34307.

Research output: Contribution to journalArticle

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