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A basolateral sorting motif in the MICA cytoplasmic tail
Hiroshi Suemizu1, Mirjana Radosavljevic, Minoru Kimura
1Department of Genetic Information, Tokai University School of Medicine, Bohseidai, Isehara 259-1193, Japan.
Summary
The MICA A5.1 allele lacks a cytoplasmic tail, causing its mislocalization in intestinal cells. This mislocalization may affect immune surveillance in epithelial cancers.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- MICA is a stress-induced glycoprotein on epithelial cells that interacts with NK and T cells.
- The common MICA A5.1 allele has a mutation causing a premature stop codon, deleting its cytoplasmic tail.
- The function of MICA and the consequences of its cytoplasmic tail deletion are not fully understood.
Purpose of the Study:
- To investigate the functional consequences of MICA cytoplasmic tail deletion.
- To determine the physiological location of MICA in human intestinal epithelium.
- To identify the role of the MICA cytoplasmic tail in protein sorting.
Main Methods:
- Expression analysis of MICA in polarized epithelial cells.
- Site-directed mutagenesis to identify sorting signals.
- Analysis of MICA A5.1 allele localization.
Main Results:
- MICA is expressed at the basolateral surface of human intestinal epithelium.
- Full-length MICA is sorted to the basolateral membrane.
- MICA with a deleted cytoplasmic tail, including the A5.1 allele, is aberrantly transported to the apical surface.
- A leucine-valine dihydrophobic tandem in the cytoplasmic tail acts as a basolateral sorting signal.
Conclusions:
- The MICA cytoplasmic tail dictates its basolateral localization in epithelial cells.
- The MICA A5.1 allele's mislocalization may impair immune surveillance in epithelial malignancies.
- Understanding MICA trafficking is crucial for epithelial cancer immunology.