Cell Reports
Volume 28, Issue 3, 16 July 2019, Pages 712-722.e3
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Article
Global Analysis of Intercellular Homeodomain Protein Transfer

https://doi.org/10.1016/j.celrep.2019.06.056Get rights and content
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Highlights

  • 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

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.

Keywords

homeodomain
cell-penetrating protein
protein secretion
intercellular protein transfer

Cited by (0)

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Present address: Korea Brain Research Institute, Daegu 41062, South Korea

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Present address: Korea Institute of Science and Technology Information, Daejeon 34141, South Korea

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