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J Biol Chem. 2018 Aug 24;293(34):13166-13175. doi: 10.1074/jbc.AC118.002052. Epub 2018 Jun 28.

Myeloid-derived growth factor is a resident endoplasmic reticulum protein.

Author information

1
From the Departments of Biomolecular Chemistry and.
2
From the Departments of Biomolecular Chemistry and dfmosher@wisc.edu.
3
Medicine, University of Wisconsin, Madison, Wisconsin 53706.

Abstract

Human myeloid-derived growth factor (MYDGF; also known as C19orf10) is named based on its identification as a secreted monocyte/macrophage-derived mediator of cardiac repair following myocardial infarction in mice. Homologs of MYDGF, however, are present in organisms throughout and outside of the animal kingdom, some of which lack hematopoietic and circulatory systems. Moreover, the UPF0556 protein domain, which defines these homologs, lacks a known structure. As a result, the functions and properties of MYDGF are unclear. Our current work was initiated to test whether MYDGF is present in secretory vesicles of eosinophils as it was recently reported to be abundant in these cells. However, we could not demonstrate secretion and unexpectedly discovered that MYDGF colocalizes with P4HB in the nuclear envelope, which comprises the bulk of endoplasmic reticulum (ER) in eosinophils, and with P4HB and RCAS1 in Golgi. We noted a ubiquitous C-terminal sequence, BXEL (B, basic; X, variable residue; E, Glu; L, Leu), that has the potential to retain human MYDGF and its homologs in the ER. To test the functionality of this sequence, we expressed full-length human MYDGF or MYDGF lacking the C-terminal Glu-Leu residues in monolayers of human embryonic kidney 293 (HEK293) cells. Full-length MYDGF accumulated in cells, whereas truncated MYDGF appeared in the medium. These observations reveal that MYDGF resides in the ER and Golgi and provide a new framework for investigating and understanding this intriguing protein.

KEYWORDS:

C19orf10; MYDGF; UPF0556; cell polarity; endoplasmic reticulum (ER); eosinophil; interleukin; protein secretion; protein sequence; protein trafficking (Golgi)

PMID:
29954947
PMCID:
PMC6109940
[Available on 2019-08-24]
DOI:
10.1074/jbc.AC118.002052

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