Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Pueyo, José I, Magny, Emile G, Sampson, Christopher J, Amin, Unum, Evans, Iwan R, Bishop, Sarah A, Couso, Juan P and Unset (2016) Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans. PLOS Biology, 14 (3). ISSN 1545-7885

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Abstract

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine
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Depositing User: Nikoleta Kiapidou
Date Deposited: 20 Apr 2016 10:58
Last Modified: 21 Sep 2017 10:31
URI: http://sro.sussex.ac.uk/id/eprint/60562

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Extension to A new Class of genes containing small Open Reading Frames: cellular and molecularG1556WELLCOME TRUST087516/Z/08/B