PUBLICATION
The evolved divergence of γ-secretase-susceptibility of homologous proteins Ngfrb and Nradd in zebrafish
- Authors
- Jayne, T., Newman, M., Baer, L., Lardelli, M.
- ID
- ZDB-PUB-211222-3
- Date
- 2021
- Source
- BMC research notes 14: 460 (Journal)
- Registered Authors
- Lardelli, Michael, Newman, Morgan
- Keywords
- Amyloid precursor protein secretases, Gene duplication, NGFR protein, Zebrafish
- MeSH Terms
-
- Amyloid Precursor Protein Secretases*/genetics
- Animals
- Apoptosis Regulatory Proteins/genetics*
- Receptor, Nerve Growth Factor/genetics*
- Zebrafish*/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 34930423 Full text @ BMC Res. Notes
Citation
Jayne, T., Newman, M., Baer, L., Lardelli, M. (2021) The evolved divergence of γ-secretase-susceptibility of homologous proteins Ngfrb and Nradd in zebrafish. BMC research notes. 14:460.
Abstract
Objective NGFR/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.
Results We 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping