Liquid–liquid phase separation facilitates the biogenesis of secretory storage granules

DOI PDF 被引用文献1件
  • Anup Parchure
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1
  • Meng Tian
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1
  • Danièle Stalder
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK 2
  • Cierra K. Boyer
    Departments of Pharmacology and Neuroscience, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 3
  • Shelby C. Bearrows
    Departments of Pharmacology and Neuroscience, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 3
  • Kristen E. Rohli
    Departments of Pharmacology and Neuroscience, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 3
  • Jianchao Zhang
    Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 5
  • Felix Rivera-Molina
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1
  • Bulat R. Ramazanov
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1
  • Sushil K. Mahata
    Department of Medicine, University of California San Diego, La Jolla, CA 7
  • Yanzhuang Wang
    Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 5
  • Samuel B. Stephens
    Departments of Pharmacology and Neuroscience, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 3
  • David C. Gershlick
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK 2
  • Julia von Blume
    Department of Cell Biology, Yale University School of Medicine, New Haven, CT 1

抄録

<jats:p>Insulin is synthesized by pancreatic β-cells and stored into secretory granules (SGs). SGs fuse with the plasma membrane in response to a stimulus and deliver insulin to the bloodstream. The mechanism of how proinsulin and its processing enzymes are sorted and targeted from the trans-Golgi network (TGN) to SGs remains mysterious. No cargo receptor for proinsulin has been identified. Here, we show that chromogranin (CG) proteins undergo liquid–liquid phase separation (LLPS) at a mildly acidic pH in the lumen of the TGN, and recruit clients like proinsulin to the condensates. Client selectivity is sequence-independent but based on the concentration of the client molecules in the TGN. We propose that the TGN provides the milieu for converting CGs into a “cargo sponge” leading to partitioning of client molecules, thus facilitating receptor-independent client sorting. These findings provide a new receptor-independent sorting model in β-cells and many other cell types and therefore represent an innovation in the field of membrane trafficking.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ