journal.pbio.1002395.pdf (16.47 MB)
Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans
journal contribution
posted on 2023-06-09, 00:59 authored by Jose Pueyo-Marques, Emile G Magny, Christopher J Sampson, Unum Amin, Iwan R Evans, Sarah Bishop, Juan Pablo CousoTranslation 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 14-3-3? 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.
Funding
Extension to A new Class of genes containing small Open Reading Frames: cellular and molecular; G1556; WELLCOME TRUST; 087516/Z/08/B
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Publication status
- Published
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- Published version
Journal
PLoS BiologyISSN
1545-7885Publisher
PLoSExternal DOI
Issue
3Volume
14Page range
1-34Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-04-20First Open Access (FOA) Date
2016-04-20First Compliant Deposit (FCD) Date
2016-04-20Usage metrics
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