Integrating phosphoproteome and transcriptome reveals new determinants of macrophage multinucleation

Maxime Rotival, Jeong-hun Ko, Prashant K. Srivastava, Audrey Kerloc'h, Alex Montoya, Claudio Mauro, Peter Faull, Pedro R. Cutillas, Enrico Petretto, Jacques Behmoaras

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
45 Downloads (Pure)

Abstract

Macrophage multinucleation (MM) is essential for various biological processes such as osteoclast-mediated bone resorption and multinucleated giant cell-associated inflammatory reactions. Here we study the molecular pathways underlying multinucleation in the rat through an integrative approach combining MS-based quantitative phosphoproteomics (LC-MS/MS) and transcriptome (high-throughput RNA-sequencing) to identify new regulators of MM. We show that a strong metabolic shift toward HIF1-mediated glycolysis occurs at transcriptomic level during MM, together with modifications in phosphorylation of over 50 proteins including several ARF GTPase activators and polyphosphate inositol phosphatases. We use shortest-path analysis to link differential phosphorylation with the transcriptomic reprogramming of macrophages and identify LRRFIP1, SMARCA4, and DNMT1 as novel regulators of MM. We experimentally validate these predictions by showing that knock-down of these latter reduce macrophage multinucleation. These results provide a new framework for the combined analysis of transcriptional and post-translational changes during macrophage multinucleation, prioritizing essential genes, and revealing the sequential events leading to the multinucleation of macrophages.
Original languageEnglish
Pages (from-to)484-498
Number of pages15
JournalMolecular and Cellular Proteomics
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2015

Fingerprint

Dive into the research topics of 'Integrating phosphoproteome and transcriptome reveals new determinants of macrophage multinucleation'. Together they form a unique fingerprint.

Cite this