The Rare TXNRD1_v3 (“v3”) Splice Variant of Human Thioredoxin Reductase 1 Protein Is Targeted to Membrane Rafts by N-Acylation and Induces Filopodia Independently of Its Redox Active Site Integrity

Abstract

Background: The TXNRD1_v3 ("v3") protein is a rare variant of human thioredoxin reductase 1. Results: Membrane targeting of v3 occurs by N-terminal myristoylation and palmitoylation, and its overexpression triggers induction of filopodia independently of its redox active site integrity. Conclusion:The v3 protein is targeted to membrane rafts. Significance: These results imply that v3, shown to be targeted to membrane rafts, may be involved in signaling events.

High‐fat diet‐induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance

“…One of TrxR1 variants has been reported to be modified by fatty acid at its N-terminal MGC motif [18] . Protein S-acylation is a common post-translational modification of proteins [19] .…”

Structural determinants of protein partitioning into ordered membrane domains and lipid rafts

“…However, in general, myristoylation is insufficient for raft targeting. Instead, a number of proteins are simultaneously myristoylated and palmitoylated, with this dual acylation efficiently promoting DRM affinity for proteins including G subunits, Src-family tyrosine kinases, reggie-1/flotillin-2, BAALC 1-6-8, UL-11 and TXNRD1-v3 (Moffett, Brown et al 2000, Mukherjee, Arnaud et al 2003, Neumann-Giesen, Falkenbach et al 2004, Wang, Tian et al 2005, Koshizuka, Kawaguchi et al 2007, Cebula, Moolla et al 2013. In surprisingand as yet unexplained -contrast with these results, myristoylated/palmitoylated constructs often do not partition efficiently into the Lo phase of GPMVs (Baumgart, Hammond et al 2007, Sengupta, Hammond et al 2008, Johnson, Stinson et al 2010.…”

Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic thioredoxin reductase and thioredoxin

“…One TrxR1 variant was reported to be palmitoylated at an Nterminal Cys residue [34] that is located outside the active site. The TrxR1 used in this study does not include the N-terminal extension.…”