Evidence map›Paper›PMID 37252981›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis.

Bryce Z Stewart, Tatyana Mamonova, W Bruce Sneddon, Airah Javorsky, Yanmei Yang, Bin Wang, Thomas D Nolin, Patrick O Humbert, Peter A Friedman, Marc Kvansakul

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
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

10 authors at 3 institutions in 2 countries.

Bryce Z StewartDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
Tatyana MamonovaLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0002-6324-0330
W Bruce SneddonLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0002-7852-8951
Airah JavorskyDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.ORCID 0000-0002-5893-6990
Yanmei YangLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Bin WangLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0002-5396-6111
Thomas D NolinDepartment of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA 15216.ORCID 0000-0003-4339-1382
Patrick O HumbertDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.ORCID 0000-0002-1366-6691
Peter A FriedmanLaboratory for GPCR Biology, Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0003-1905-1468
Marc KvansakulDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.ORCID 0000-0003-2639-2498
University of Pittsburgh · USLa Trobe University · AUThe University of Melbourne · AU

Funding

Functional Polarity of PTH Receptor Signaling: Cellular and Molecular MechanismsR01DK111427 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRIEDMAN, PETER A, VILARDAGA, JEAN-PIERRE · 2017 to 2020
$2.4M
NIDDK NIH HHS R01 DK111427
6 · The paper itself

Abstract

G protein-coupled receptors, including PTHR, are pivotal for controlling metabolic processes ranging from serum phosphate and vitamin D levels to glucose uptake, and cytoplasmic interactors may modulate their signaling, trafficking, and function. We now show that direct interaction with Scribble, a cell polarity-regulating adaptor protein, modulates PTHR activity. Scribble is a crucial regulator for establishing and developing tissue architecture, and its dysregulation is involved in various disease conditions, including tumor expansion and viral infections. Scribble co-localizes with PTHR at basal and lateral surfaces in polarized cells. Using X-ray crystallography, we show that colocalization is mediated by engaging a short sequence motif at the PTHR C-terminus using Scribble PDZ1 and PDZ3 domain, with binding affinities of 31.7 and 13.4 μM, respectively. Since PTHR controls metabolic functions by actions on renal proximal tubules, we engineered mice to selectively knockout Scribble in proximal tubules. The loss of Scribble impacted serum phosphate and vitamin D levels and caused significant plasma phosphate elevation and increased aggregate vitamin D

Indexed as

PhosphatesVitamin DAnimalsHomeostasisIntracellular Signaling Peptides and ProteinsMiceParathyroid HormoneProtein BindingReceptor, Parathyroid Hormone, Type 1Receptors, Parathyroid HormoneVitaminsIntracellular Signaling Peptides and ProteinsParathyroid HormonePhosphatesReceptor, Parathyroid Hormone, Type 1Receptors, Parathyroid Hormonescrib protein, mouseVitamin DVitaminscell polarityGPCRphosphate homeostasisPTHRScribble

Identifiers

PMID37252981
PMCPMC10266016
OpenAlexW4378783067

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.