Cell metabolism regulates integrin mechanosensing via an SLC3A2-dependent sphingolipid biosynthesis pathway

• DOI: 10.1038/s41467-018-07268-w
• Publication Date: 2018-11-13T14:54:17Z
• Authors: Etienne Boulter; Soline Estrach; Floriane S. Tissot; Marco L. Hennrich; Lionel Tosello; Laurence Cailleteau; Laura R. de la Ba...; Sabrina Pisano; Anne-Claude Gavin; Chloé C. Féral
• Keywords: Sphingolipid; Cell metabolism

Abstract Mechanical and metabolic cues independently contribute to the regulation of cell tissue homeostasis. However, how they cross-regulate each other during this process remains largely unknown. Here, we show that cellular metabolism can regulate integrin rigidity-sensing via sphingolipid pathway controlled by amino acid transporter coreceptor CD98hc (SLC3A2). Genetic invalidation in dermal cells impairs rigidity sensing mechanical signaling downstream integrins, including RhoA activation, resulting aberrant Unexpectedly, found does not occur directly through integrins but indirectly, synthesis delta-4-desaturase DES2. Loss decreases availability preventing proper membrane recruitment, shuttling activation upstream regulators Src kinases GEF-H1. Altogether, our results unravel a novel cross-talk between mechanosensing which may constitute an important new regulatory framework contributing