A novel class of er membrane proteins regulates ER-associated endosome fission

• Melissa J. Hoyer ^[1] ; Patrick J. Chitwood ^[1] ; Christopher C. Ebmeier ^[1]
  1. [1] University of Colorado Boulder

     University of Colorado Boulder

     Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 175, Nº. 1, 2018, págs. 254-265
• Idioma: inglés
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• Resumen

  • Endoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of a conserved protein family. TMCC1 concentrates at the ER-endosome MCSs that are spatially and temporally linked to endosome fission. When TMCC1 is depleted, endosome morphology is normal, buds still form, but ER-associated bud fission and subsequent cargo sorting to the Golgi are impaired. We find that the endosome-localized actin regulator Coronin 1C is required for ER-associated fission of actin-dependent cargo-sorting domains. Coronin 1C is recruited to endosome buds independently of TMCC1, while TMCC1/ER recruitment requires Coronin 1C. This link between TMCC1 and Coronin 1C suggests that the timing of TMCC1-dependent ER recruitment is tightly regulated to occur after cargo has been properly sequestered into the bud.