Eps8, Arp2/3 and IRSp53 in TNT formation
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ABSTRACT: Tunneling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How the cell controls a common pool of proteins to generate these protrusions spanning length scales beyond those attainable by canonical filopodia remains unknown. Through a combination of surface micropatterning and optical tweezer-based approaches, we found that Arp2/3-dependent pathways attenuate the extent with which actin polymerizes in nanotubes, limiting the formation and attainable lengths of TNTs. Proteomic analysis using Epidermal growth factor receptor kinase substrate 8 (Eps8) as a positive effector of TNTs showed that upon Arp2/3 inhibition, proteins enhancing filament turnover and depolymerization were reduced and instead Eps8 exhibited heightened interactions with the inverted Bin/Amphiphysin/Rvs (I-BAR) domain protein IRSp53 that provides a direct connection with linear actin polymerases. Our data reveals how common players in protrusions (Eps8 and IRSp53) facilitate the formation of TNTs, and that this Eps-IRSp53 interaction is enhanced when competing pathways overutilizing actin in branched Arp2/3 networks are inhibited to drive outward actin extension.
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (mouse)
SUBMITTER: MARIETTE MATONDO
LAB HEAD: Michael Henderson
PROVIDER: PXD034649 | Pride | 2023-11-27
REPOSITORIES: Pride
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