title: Knockdown of beta2-microglobulin perturbs the subcellular distribution of HFE and hepcidin.
abstract: Hereditary Haemochromatosis is an iron overload disorder associated with mutations in the HFE gene, and to a lesser degree, the gene encoding its chaperone protein beta-2 microglobulin (beta2M). Here, we report that knockdown of beta2M by RNAi restricts HFE distribution to the endoplasmic reticulum (ER). Additionally, we demonstrate that hepcidin, an iron homeostasis-associated protein, localises predominantly to LBPA-positive late endosomes. Interestingly, we show that knockdown of beta2M by RNAi perturbs hepcidin localisation to late endosomes. In summary, our data suggest that beta2M is essential for the correct subcellular distribution of both HFE and hepcidin, two proteins, which are critical for iron homeostasis.
authors.affiliation: Department of Biochemistry, Molecular Cell Biology Laboratory, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Bhatt
authors.forename: Conor P
authors.initials: CP
authors.lastname: Horgan
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D001613:beta 2-Microglobulin / Q000235:genetics*
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D001613:beta 2-Microglobulin