Global Analysis of Intercellular Homeodomain Protein Transfer.
Amino Acid Motifs
/ genetics
Animals
Brain
/ embryology
Cell Communication
/ genetics
Cell Line
Female
High-Throughput Screening Assays
Homeodomain Proteins
/ genetics
Humans
Hydrophobic and Hydrophilic Interactions
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Pregnancy
Protein Transport
/ genetics
Retina
/ metabolism
cell-penetrating protein
homeodomain
intercellular protein transfer
protein secretion
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 07 2019
16 07 2019
Historique:
received:
02
11
2018
revised:
06
05
2019
accepted:
14
06
2019
entrez:
18
7
2019
pubmed:
18
7
2019
medline:
28
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31315049
pii: S2211-1247(19)30829-0
doi: 10.1016/j.celrep.2019.06.056
pmc: PMC9472292
mid: NIHMS1832618
pii:
doi:
Substances chimiques
Homeodomain Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
712-722.e3Subventions
Organisme : NEI NIH HHS
ID : R01 EY020560
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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