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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

journal contribution
posted on 2023-06-09, 07:38 authored by Alice CopseyAlice Copsey, Simon Cooper, Robert Parker, Ella Lineham, Cuzack Lapworth, Deema Basil Sadiq JALLAD, Steve Sweet, Simon Morley
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.

Funding

The re-modelling of mRNPs and the regulation of localised mRNA translation during mammalian cell attachment and spreading; G1479; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/L018209/1

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Biochemical Journal

ISSN

0264-6021

Publisher

Portland Press

Issue

18

Volume

474

Page range

3109-3120

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2017-08-16

First Open Access (FOA) Date

2017-08-16

First Compliant Deposit (FCD) Date

2017-08-16

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