1. A role for the MHC class I-like Mill molecules in nutrient metabolism and wound healing
- Author
-
David Cosman, Lynn Goldstein, Brian A Rabinovich, Randal R. Ketchem, Martin Wolfson, and Marylin Skelly
- Subjects
Subfamily ,T-Lymphocytes ,Immunology ,Antigen presentation ,Blotting, Western ,Green Fluorescent Proteins ,Myocytes, Smooth Muscle ,Genes, MHC Class I ,Thymus Gland ,Biology ,Mice ,Organ Culture Techniques ,MHC class I ,Immunology and Allergy ,Animals ,Computer Simulation ,Cloning, Molecular ,Hemochromatosis Protein ,Cell Proliferation ,Skin ,Mice, Inbred BALB C ,Wound Healing ,Membrane Glycoproteins ,Histocompatibility Antigens Class I ,Uterus ,Membrane Proteins ,Cell Biology ,Fibroblasts ,Ligand (biochemistry) ,NKG2D ,Flow Cytometry ,Rats ,Alternative Splicing ,Biochemistry ,Rats, Inbred Lew ,biology.protein ,Female ,Antibody ,Wound healing ,beta 2-Microglobulin ,Function (biology) - Abstract
MHC class I family members serve multiple functions beyond antigen presentation. We provide insight into the structure, expression and function of the Mill subfamily. This family includes two surface glycoproteins, Mill1 and Mill2. Protein sequences for Mill1 and Mill2 are most highly related to the NKG2D ligands, MICA and MICB, but neither of them bound to NKG2D. Computer-based protein modelling indicated that hereditary haemochromatosis protein (HFE), a molecule involved in iron uptake, was most similar. Mill1 and Mill2 were observed on cycling thymocytes, proliferating smooth muscle cells and fibroblasts. Using soluble Mill proteins, we found evidence for a soluble ligand in serum. Like HFE, the Mill family may be involved in nutrient metabolism. Skin was one of the only three organs found to express transcripts for both Mill1 and Mill2. Addition of antibodies specific for Mill2 to wounded skin enhanced healing. Our results suggest a role for the Mill proteins in cellular metabolism, with possible therapeutic significance.
- Published
- 2008