The helicase, DDX3X, interacts with poly(A) binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading

Copsey, Alice C, Cooper, Simon, Parker, Robert, Lineham, Ella, Lapworth, Cuzack, JALLAD, Deema Basil Sadiq, Sweet, Steve and Morley, Simon J (2017) The helicase, DDX3X, interacts with poly(A) binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading. Biochemical Journal. ISSN 0264-6021 (Accepted)

[img] PDF - Accepted Version
Restricted to SRO admin only until 21 July 2018.
Available under License Creative Commons Attribution.

Download (1MB)

Abstract

DDX3X, a helicase, can interact directly with mRNA and translation initiation factors, regulating the selective translation of mRNAs that contain a structured 5′ untranslated region (5’UTR). This activity modulates the expression of mRNAs controlling cell cycle progression and mRNAs regulating actin dynamics, contributing to cell adhesion and motility. Previously, we have shown that ribosomes and translation initiation factors localise to the leading edge of migrating fibroblasts in loci enriched with actively translating ribosomes, thereby promoting steady-state levels of ArpC2 and Rac1 proteins at the leading edge of cells during spreading. As DDX3X can regulate Rac1 levels, cell motility and metastasis, we have examined DDX3X protein interactions and localisation using a number of complementary approaches. We now show that DDX3X can physically interact and co-localise with PABP1 and caprin-1 at the leading edge of spreading cells. Furthermore, as depletion of DDX3X leads to decreased cell motility, this provides a functional link between DDX3X, caprin-1 and initiation factors at the leading edge of migrating cells to promote cell migration and spreading.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Simon Morley
Date Deposited: 16 Aug 2017 10:45
Last Modified: 24 Aug 2017 16:12
URI: http://sro.sussex.ac.uk/id/eprint/69791

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
The re-modelling of mRNPs and the regulation of localised mRNA translation during mammalian cell attachment and spreadingG1479BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/L018209/1