Evidence map›Paper›PMID 33153264›Full record

ArticleBiochemistry2020

An Allosteric Binding Site on Sortilin Regulates the Trafficking of VLDL, PCSK9, and LDLR in Hepatocytes.

Robert P Sparks, Andres S Arango, Jermaine L Jenkins, Wayne C Guida, Emad Tajkhorshid, Charles E Sparks, Janet D Sparks, Rutilio A Fratti

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Robert P SparksDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.
Andres S ArangoCenter for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0003-2278-3619
Jermaine L JenkinsStructural Biology & Biophysics Facility, University of Rochester Medical Center, Rochester, New York 14642, United States.
Wayne C GuidaDepartment of Chemistry, University of South Florida, Tampa, Florida 33620, United States.
Emad TajkhorshidDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0001-8434-1010
Charles E SparksDepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, United States.
Janet D SparksDepartment of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, United States.
Rutilio A FrattiDepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.ORCID 0000-0001-9109-6666
University of Illinois Urbana-Champaign · USUniversity of Rochester Medical Center · USUniversity of South Florida · US

Funding

Synthetic Antigen Binder CoreU54GM087519 · NIGMS · UNIVERSITY OF CHICAGO · PI NAKAMOTO, ROBERT K. · 2010 to 2017
$31.9M
WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI SCHULTEN, KLAUS · 2012 to 2021
$19.0M
Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
Multi-scale modeling of gas transport through channels in living cellsU01GM111251 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI BORON, WALTER F, SOMERSALO, ERKKI JAAKKO · 2015 to 2019
$2.9M
Allosteric Regulation of SNAREs and the Rab GEF Mon1 by PhosphoinositidesR01GM101132 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI FRATTI, RUTILIO A · 2012 to 2016
$1.4M
BIAcore T100 for research and drug discovery in RochesterS10RR027241 · NCRR · UNIVERSITY OF ROCHESTER · PI KIELKOPF, CLARA · 2010 to 2010
$365k
NCRR NIH HHS S10 RR027241NIAID NIH HHS P30 AI078498NIGMS NIH HHS P41 GM104601NIGMS NIH HHS R01 GM101132NIGMS NIH HHS U01 GM111251NIGMS NIH HHS U54 GM087519
6 · The paper itself

Abstract

ApoB lipoproteins (apo B-Lp) are produced in hepatocytes, and their secretion requires the cargo receptor sortilin. We examined the secretion of apo B-Lp-containing very low-density lipoprotein (VLDL), an LDL progenitor. Sortilin also regulates the trafficking of the subtilase PCSK9, which when secreted binds the LDL receptor (LDLR), resulting in its endocytosis and destruction at the lysosome. We show that the site 2 binding compound (cpd984) has multiple effects in hepatocytes, including (1) enhanced Apo-Lp secretion, (2) increased cellular PCSK9 retention, and (3) augmented levels of LDLR at the plasma membrane. We postulate that cpd984 enhances apo B-Lp secretion in part through binding the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP

Indexed as

Adaptor Proteins, Vesicular TransportAllosteric RegulationAnimalsBinding SitesHepatocytesHumansLipoproteins, VLDLMolecular Dynamics SimulationProprotein Convertase 9Protein ConformationProtein TransportRatsRats, Sprague-DawleyReceptors, LDLSortilinAdaptor Proteins, Vesicular TransportLipoproteins, VLDLProprotein Convertase 9Receptors, LDLSortilin

Identifiers

PMID33153264
PMCPMC7674269
OpenAlexW3096194094

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.