Global Analysis of Intercellular Homeodomain Protein Transfer
The homeodomain is found in hundreds of transcription factors that play roles in fate determination via cell-autonomous regulation of gene expression. However, some homeodomain-containing proteins (HPs) are thought to be secreted and penetrate neighboring cells to affect the recipient cell fate. To...
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Published in | Cell reports (Cambridge) Vol. 28; no. 3; pp. 712 - 722.e3 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
16.07.2019
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | The homeodomain is found in hundreds of transcription factors that play roles in fate determination via cell-autonomous regulation of gene expression. However, some homeodomain-containing proteins (HPs) are thought to be secreted and penetrate neighboring cells to affect the recipient cell fate. To determine whether this is a general characteristic of HPs, we carried out a large-scale validation for intercellular transfer of HPs. Our screening reveals that intercellular transfer is a general feature of HPs, but it occurs in a cell-context-sensitive manner. We also found the secretion is not solely a function of the homeodomain, but it is supported by external motifs containing hydrophobic residues. Thus, mutations of hydrophobic residues of HPs abrogate secretion and consequently interfere with HP function in recipient cells. Collectively, our study proposes that HP transfer is an intercellular communication method that couples the functions of interacting cells.
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•Intercellular transfer is a general feature of homeodomain proteins (HPs)•HP secretion is a cell-context-sensitive event•Hydrophobic residues outside of the homeodomain support the secretion of HP
Lee et al. evaluate capabilities of homeodomain proteins (HPs) for transfer between cells. They find that intercellular transfer is a general but cell-context-sensitive property of HP. Intercellular HP transfer can be an unconventional way for the cells to communicate with neighboring cells that associate structurally and functionally. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS E.J.L. designed, performed, and analyzed the experiments shown in all figures and supplemental figures and wrote and revised the manuscript. N.K. performed explants experiments. J.W.P. and K.H.K. performed and analyzed DB, WB, and immunostaining of HPs with the samples. W.K. and N.S.S. performed in utero electroporation. C.-S.J. performed comparative analyses of amino acid sequences of HPs. S.B. and M.V. provided resources used in this study. S.-O.H., D.K., and J.H.L. supervised the analyses and commented on the manuscript. J.W.K. (corresponding author) wrote the original draft and revised the manuscript, conceived and supervised the study, and secured funding for this study. |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2019.06.056 |