Abstract
Exosomes are nanoscale vesicles that mediate intercellular communication. Cellular exosome uptake mechanisms are not well defined partly due to the lack of specific inhibitors of this complex cellular process. Exosome uptake depends on cholesterol-rich membrane microdomains called lipid rafts, and can be blocked by non-specific depletion of plasma membrane cholesterol. Scavenger receptor type B-1 (SR-B1), found in lipid rafts, is a receptor for cholesterol-rich high-density lipoproteins (HDL). We hypothesized that a synthetic nanoparticle mimic of HDL (HDL NP) that binds SR-B1 and removes cholesterol through this receptor would inhibit cellular exosome uptake. In cell models, our data show that HDL NPs bind SR-B1, activate cholesterol efflux, and attenuate the influx of esterified cholesterol. As a result, HDL NP treatment results in decreased dynamics and clustering of SR-B1 contained in lipid rafts and potently inhibits cellular exosome uptake. Thus, SR-B1 and targeted HDL NPs provide a fundamental advance in studying cholesterol-dependent cellular uptake mechanisms.
| Original language | English (US) |
|---|---|
| Article number | 15724 |
| Journal | Scientific reports |
| Volume | 5 |
| DOIs | |
| State | Published - Oct 29 2015 |
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ASJC Scopus subject areas
- General
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Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake. / Plebanek, Michael P.; Mutharasan, R. Kannan; Volpert, Olga; Matov, Alexandre; Gatlin, Jesse C.; Thaxton, C. Shad.
In: Scientific reports, Vol. 5, 15724, 29.10.2015.Research output: Contribution to journal › Article
TY - JOUR
T1 - Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake
AU - Plebanek, Michael P.
AU - Mutharasan, R. Kannan
AU - Volpert, Olga
AU - Matov, Alexandre
AU - Gatlin, Jesse C.
AU - Thaxton, C. Shad
PY - 2015/10/29
Y1 - 2015/10/29
N2 - Exosomes are nanoscale vesicles that mediate intercellular communication. Cellular exosome uptake mechanisms are not well defined partly due to the lack of specific inhibitors of this complex cellular process. Exosome uptake depends on cholesterol-rich membrane microdomains called lipid rafts, and can be blocked by non-specific depletion of plasma membrane cholesterol. Scavenger receptor type B-1 (SR-B1), found in lipid rafts, is a receptor for cholesterol-rich high-density lipoproteins (HDL). We hypothesized that a synthetic nanoparticle mimic of HDL (HDL NP) that binds SR-B1 and removes cholesterol through this receptor would inhibit cellular exosome uptake. In cell models, our data show that HDL NPs bind SR-B1, activate cholesterol efflux, and attenuate the influx of esterified cholesterol. As a result, HDL NP treatment results in decreased dynamics and clustering of SR-B1 contained in lipid rafts and potently inhibits cellular exosome uptake. Thus, SR-B1 and targeted HDL NPs provide a fundamental advance in studying cholesterol-dependent cellular uptake mechanisms.
AB - Exosomes are nanoscale vesicles that mediate intercellular communication. Cellular exosome uptake mechanisms are not well defined partly due to the lack of specific inhibitors of this complex cellular process. Exosome uptake depends on cholesterol-rich membrane microdomains called lipid rafts, and can be blocked by non-specific depletion of plasma membrane cholesterol. Scavenger receptor type B-1 (SR-B1), found in lipid rafts, is a receptor for cholesterol-rich high-density lipoproteins (HDL). We hypothesized that a synthetic nanoparticle mimic of HDL (HDL NP) that binds SR-B1 and removes cholesterol through this receptor would inhibit cellular exosome uptake. In cell models, our data show that HDL NPs bind SR-B1, activate cholesterol efflux, and attenuate the influx of esterified cholesterol. As a result, HDL NP treatment results in decreased dynamics and clustering of SR-B1 contained in lipid rafts and potently inhibits cellular exosome uptake. Thus, SR-B1 and targeted HDL NPs provide a fundamental advance in studying cholesterol-dependent cellular uptake mechanisms.
UR - http://www.scopus.com/inward/record.url?scp=84946113945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946113945&partnerID=8YFLogxK
U2 - 10.1038/srep15724
DO - 10.1038/srep15724
M3 - Article
C2 - 26511855
AN - SCOPUS:84946113945
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 15724
ER -