Evidence map›Paper›PMID 27808165›Full record

ArticleScientific reports2016

Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.

Faiza Baameur, Pooja Singhmar, Yong Zhou, John F Hancock, Xiaodong Cheng, Cobi J Heijnen, Annemieke Kavelaars

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.5field-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

15 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

7 authors at 2 institutions in 1 country.

Faiza BaameurLaboratory of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pooja SinghmarLaboratory of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yong ZhouDepartment of Integrative Biology and Pharmacology and Texas Therapeutics Institute, The University of Texas Health Science Center, Houston, TX 77030, USA.
John F HancockDepartment of Integrative Biology and Pharmacology and Texas Therapeutics Institute, The University of Texas Health Science Center, Houston, TX 77030, USA.
Xiaodong ChengDepartment of Integrative Biology and Pharmacology and Texas Therapeutics Institute, The University of Texas Health Science Center, Houston, TX 77030, USA.
Cobi J HeijnenLaboratory of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Annemieke KavelaarsLaboratory of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center · USThe University of Texas Health Science Center at Houston · US

Funding

Epac/cAMP-GEF, A Novel Intracellular cAMP ReceptorR01GM066170 · NIGMS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI CHENG, XIAODONG · 2003 to 2017
$4.6M
Neuroimmune Mechanisms of Recovery from Comorbid Depression and Chronic PainR01NS073939 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DANTZER, ROBERT, HEIJNEN, COBI J · 2011 to 2020
$4.0M
NIGMS NIH HHS R01 GM066170NINDS NIH HHS R01 NS073939
6 · The paper itself

Abstract

Exchange protein directly activated by cAMP-1 (Epac1) is a cAMP sensor that regulates multiple cellular functions including cellular migration, proliferation and differentiation. Classically, Epac1 is thought to exert its effects through binding of cAMP leading to a conformational change in Epac1 and its accumulation at the plasma membrane (PM) where it activates Rap1. In search for regulators of Epac1 activity, we show here that importin β1 (impβ1) is an Epac1 binding partner that prevents PM accumulation of Epac1. We demonstrate that in the absence of impβ1, endogenous as well as overexpressed Epac1 accumulate at the PM. Moreover, agonist-induced PM translocation of Epac1 leads to dissociation of Epac1 from impβ1. Localization of Epac1 at the PM in the absence of impβ1, requires residue R82 in its DEP domain. Notably, the PM accumulation of Epac1 in the absence of impβ1 does not require binding of cAMP to Epac1 and does not result in Rap1 activation. Functionally, PM accumulation of Epac1, an Epac1 mutant deficient in cAMP binding, or an Epac1 mutant tethered to the PM, is sufficient to inhibit neurite outgrowth. In conclusion, we uncover a cAMP-independent function of Epac1 at the PM and demonstrate that impβ1 controls subcellular localization of Epac1.

Indexed as

Neuronal Outgrowthbeta KaryopherinsCell LineCell MembraneCyclic AMPGuanine Nucleotide Exchange FactorsHEK293 CellsHumansProteomicsrap1 GTP-Binding Proteinsbeta KaryopherinsCyclic AMPGuanine Nucleotide Exchange FactorsKPNB1 protein, humanrap1 GTP-Binding ProteinsRAPGEF3 protein, human

Identifiers

PMID27808165
PMCPMC5093460
OpenAlexW2548903266

What Socratic holds

Textmetadata
LicenceCC BY
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.