Evidence map›Paper›PMID 34930423›Full record

ArticleBMC research notes2021

The evolved divergence of γ-secretase-susceptibility of homologous proteins Ngfrb and Nradd in zebrafish.

Tanya Jayne, Morgan Newman, Lachlan Baer, Michael Lardelli

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Article in BMC research notes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Tanya JayneDepartment of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia.
Morgan NewmanDepartment of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia.
Lachlan BaerDepartment of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia.
Michael LardelliDepartment of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia. michael.lardelli@adelaide.edu.au.ORCID http://orcid.org/0000-0002-4289-444X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveNGFR/p75NTR and NRADD/NRH proteins are closely related structurally and are encoded by genes that arose from a duplication event early in vertebrate evolution. The transmembrane domain (TMD) of NGFR is cleaved by γ-secretase but there is conflicting data around the susceptibility to γ-secretase cleavage of NRADD proteins. If NGFR and NRADD show differential susceptibility to γ-secretase, then they can be used to dissect the structural constraints determining substrate susceptibility. We sought to test this differential susceptibility.

resultsWe developed labelled, lumenally-truncated forms of zebrafish Ngfrb and Nradd and a chimeric protein in which the TMD of Nradd was replaced with the TMD of Ngfrb. We expressed these in zebrafish embryos to test their susceptibility to γ-secretase cleavage by monitoring their stability using western immunoblotting. Inhibition of γ-secretase activity using DAPT increased the stability of only the Ngfrb construct. Our results support that only NGFR is cleaved by γ-secretase. Either NGFR evolved γ-secretase-susceptibility since its creation by gene duplication, or NRADD evolved to be refractory to γ-secretase. Protein structure outside of the TMD of NGFR is likely required for susceptibility to γ-secretase.

Indexed as

Amyloid Precursor Protein SecretasesZebrafishAnimalsApoptosis Regulatory ProteinsReceptor, Nerve Growth FactorZebrafish ProteinsAmyloid Precursor Protein SecretasesApoptosis Regulatory Proteinsnradd protein, zebrafishReceptor, Nerve Growth FactorZebrafish ProteinsAmyloid precursor protein secretasesGene duplicationNGFR proteinZebrafish

Identifiers

PMID34930423
PMCPMC8686249

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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.