Evidence map›Paper›PMID 24184645›Full record

ArticleChemistry and physics of lipids2014

The C2 domains of granuphilin are high-affinity sensors for plasma membrane lipids.

Tatyana A Lyakhova, Jefferson D Knight

Abstract read
In one paragraph

Article in Chemistry and physics of lipids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 29% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 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

2 authors at 1 institution in 1 country.

Tatyana A LyakhovaDepartment of Chemistry, University of Colorado Denver, Campus Box 194, P.O. Box 173364, Denver, CO 80217, USA.
Jefferson D KnightDepartment of Chemistry, University of Colorado Denver, Campus Box 194, P.O. Box 173364, Denver, CO 80217, USA. Electronic address: jefferson.knight@ucdenver.edu.
University of Colorado Denver · US

Funding

MBRS-IMSD Program at the University of Colorado at Denver and Health Sciences CenR25GM083333 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI FLORES, SONIA CASTRO · 2008 to 2012
$1.5M
NIGMS NIH HHS 5R25GM083333NIGMS NIH HHS R25 GM083333
6 · The paper itself

Abstract

Membrane-targeting proteins are crucial components of many cell signaling pathways, including the secretion of insulin. Granuphilin, also known as synaptotagmin-like protein 4, functions in tethering secretory vesicles to the plasma membrane prior to exocytosis. Granuphilin docks to insulin secretory vesicles through interaction of its N-terminal domain with vesicular Rab proteins; however, the mechanisms of granuphilin plasma membrane targeting and release are less clear. Granuphilin contains two C2 domains, C2A and C2B, that interact with the plasma membrane lipid phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. The goal of this study was to determine membrane-binding mechanisms, affinities, and kinetics of both granuphilin C2 domains using fluorescence spectroscopic techniques. Results indicate that both C2A and C2B bind anionic lipids in a Ca(2+)-independent manner. The C2A domain binds liposomes containing a physiological mixture of lipids including 2% PI(4,5)P2 or PI(3,4,5)P3 with high affinity (apparent K(d, PIPx) of 2-5 nM), and binds nonspecifically with moderate affinity to anionic liposomes lacking phosphatidylinositol phosphate (PIPx) lipids. The C2B domain binds with sub-micromolar affinity to liposomes containing PI(4,5)P2 but does not have a measurable affinity for background anionic lipids. Both domains can be competed away from their target lipids by the soluble PIPx analog inositol-(1,2,3,4,5,6)-hexakisphosphate (IP6), which is a positive regulator of insulin secretion. Potential roles of these interactions in the docking and release of granuphilin from the plasma membrane are discussed.

Indexed as

Binding, CompetitiveCell MembraneHumansInsulinInsulin SecretionKineticsMembrane LipidsModels, MolecularPhosphatidylinositol PhosphatesPhytic AcidProtein BindingProtein Structure, TertiaryVesicular Transport ProteinsInsulinMembrane Lipidsphosphatidylinositol 3,4,5-triphosphatePhosphatidylinositol PhosphatesPhytic AcidSYTL4 protein, humanVesicular Transport ProteinsInositol polyphosphate signalingInsulin secretionPhosphatidylinositol-(4,5)-bisphosphateProtein–lipid interactionSecretory granule dockingSlp4

Identifiers

PMID24184645
PMCPMC4085138
OpenAlexW2041073866

What OpenQuestion holds

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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 OpenQuestion graph.