PMID- 30956133
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20231012
IS  - 2211-1247 (Electronic)
VI  - 27
IP  - 3
DP  - 2019 Apr 16
TI  - Transfer of Functional Cargo in Exomeres.
PG  - 940-954.e6
LID - S2211-1247(19)30017-8 [pii]
LID - 10.1016/j.celrep.2019.01.009 [doi]
AB  - Exomeres are a recently discovered type of extracellular nanoparticle with no 
      known biological function. Herein, we describe a simple ultracentrifugation-based 
      method for separation of exomeres from exosomes. Exomeres are enriched in 
      Argonaute 1-3 and amyloid precursor protein. We identify distinct functions of 
      exomeres mediated by two of their cargo, the beta-galactoside alpha2,6-sialyltransferase 
      1 (ST6Gal-I) that alpha2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin 
      (AREG). Functional ST6Gal-I in exomeres can be transferred to cells, resulting in 
      hypersialylation of recipient cell-surface proteins including beta1-integrin. 
      AREG-containing exomeres elicit prolonged EGFR and downstream signaling in 
      recipient cells, modulate EGFR trafficking in normal intestinal organoids, and 
      dramatically enhance the growth of colonic tumor organoids. This study provides a 
      simplified method of exomere isolation and demonstrates that exomeres contain and 
      can transfer functional cargo. These findings underscore the heterogeneity of 
      nanoparticles and should accelerate advances in determining the composition and 
      biological functions of exomeres.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Zhang, Qin
AU  - Zhang Q
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Higginbotham, James N
AU  - Higginbotham JN
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Jeppesen, Dennis K
AU  - Jeppesen DK
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Yang, Yu-Ping
AU  - Yang YP
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Li, Wei
AU  - Li W
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - McKinley, Eliot T
AU  - McKinley ET
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Graves-Deal, Ramona
AU  - Graves-Deal R
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA.
FAU - Ping, Jie
AU  - Ping J
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Britain, Colleen M
AU  - Britain CM
AD  - Cell, Developmental and Integrative Biology (CDIB), School of Medicine, 
      University of Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Dorsett, Kaitlyn A
AU  - Dorsett KA
AD  - Cell, Developmental and Integrative Biology (CDIB), School of Medicine, 
      University of Alabama at Birmingham, Birmingham, AL 35233, USA.
FAU - Hartman, Celine L
AU  - Hartman CL
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology and Center for 
      Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 
      63104, USA.
FAU - Ford, David A
AU  - Ford DA
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology and Center for 
      Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO 
      63104, USA.
FAU - Allen, Ryan M
AU  - Allen RM
AD  - Department of Cardiology, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Vickers, Kasey C
AU  - Vickers KC
AD  - Department of Cardiology, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Liu, Qi
AU  - Liu Q
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Franklin, Jeffrey L
AU  - Franklin JL
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA; Cell and Developmental 
      Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Veterans 
      Affairs Medical Center, Nashville, Vanderbilt University, TN 37212, USA.
FAU - Bellis, Susan L
AU  - Bellis SL
AD  - Cell, Developmental and Integrative Biology (CDIB), School of Medicine, 
      University of Alabama at Birmingham, Birmingham, AL 35233, USA. Electronic 
      address: bellis@uab.edu.
FAU - Coffey, Robert J
AU  - Coffey RJ
AD  - Department of Medicine/Gastroenterology and Epithelial Biology Center, Vanderbilt 
      University Medical Center, Nashville, TN 37232, USA; Cell and Developmental 
      Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Veterans 
      Affairs Medical Center, Nashville, Vanderbilt University, TN 37212, USA. 
      Electronic address: robert.coffey@vumc.org.
LA  - eng
GR  - K22 HL113039/HL/NHLBI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA046413/CA/NCI NIH HHS/United States
GR  - R35 CA197570/CA/NCI NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - R01 HL127173/HL/NHLBI NIH HHS/United States
GR  - U19 CA179514/CA/NCI NIH HHS/United States
GR  - R01 HL128996/HL/NHLBI NIH HHS/United States
GR  - UG3 CA241685/CA/NCI NIH HHS/United States
GR  - R01 CA225177/CA/NCI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - R01 CA163563/CA/NCI NIH HHS/United States
GR  - P01 HL116263/HL/NHLBI NIH HHS/United States
GR  - P50 CA236733/CA/NCI NIH HHS/United States
GR  - T32 GM008111/GM/NIGMS NIH HHS/United States
GR  - R01 GM111093/GM/NIGMS NIH HHS/United States
GR  - U01 CA233581/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190404
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Amphiregulin)
RN  - 0 (Lipids)
RN  - 0 (Nucleic Acids)
RN  - 0 (Proteome)
RN  - EC 2.4.99.- (Sialyltransferases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.4.99.1 (beta-D-Galactoside alpha 2-6-Sialyltransferase)
SB  - IM
MH  - Amphiregulin/genetics/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/metabolism/pathology
MH  - Dogs
MH  - ErbB Receptors/chemistry/metabolism
MH  - Exosomes/chemistry/*metabolism
MH  - Humans
MH  - Lipids/analysis/chemistry
MH  - Madin Darby Canine Kidney Cells
MH  - Mice
MH  - Mice, Knockout
MH  - Nanoparticles/chemistry/*metabolism
MH  - Nucleic Acids/analysis
MH  - Particle Size
MH  - Principal Component Analysis
MH  - Proteome/analysis/metabolism
MH  - Proteomics/methods
MH  - Sialyltransferases/analysis/metabolism
MH  - beta-D-Galactoside alpha 2-6-Sialyltransferase
PMC - PMC6559347
MID - NIHMS1527182
OTO - NOTNLM
OT  - Argonautes
OT  - EGFR
OT  - ST6Gal-I
OT  - amphiregulin
OT  - exomeres
OT  - exosomes
OT  - extracellular vesicles
OT  - fluorescence-activated vesicle sorting
OT  - organoids
OT  - beta1-integrin
COIS- DECLARATION OF INTERESTS The authors declare no competing interests.
EDAT- 2019/04/09 06:00
MHDA- 2020/06/17 06:00
PMCR- 2019/06/11
CRDT- 2019/04/09 06:00
PHST- 2018/06/29 00:00 [received]
PHST- 2018/11/02 00:00 [revised]
PHST- 2019/01/02 00:00 [accepted]
PHST- 2019/04/09 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/04/09 06:00 [entrez]
PHST- 2019/06/11 00:00 [pmc-release]
AID - S2211-1247(19)30017-8 [pii]
AID - 10.1016/j.celrep.2019.01.009 [doi]
PST - ppublish
SO  - Cell Rep. 2019 Apr 16;27(3):940-954.e6. doi: 10.1016/j.celrep.2019.01.009. Epub 
      2019 Apr 4.