A model for collagen secretion by intercompartmental continuities

• 成果类型: Article
• 署名作者: Bunel, Louis; Pincet, Lancelot; Malhotra, Vivek; Raote, Ishier; Pincet, Frederic
• 署名单位: Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; Universite PSL; Ecole Normale Superieure (ENS); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; ICREA; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13755
• DOI: 10.1073/pnas.2310404120
• 发表日期: 2024-01-02
• 关键词: triple-helix; ph; protein; hsp47; procollagen; mechanisms; molecule; sites; FORCE

摘要

Newly synthesized secretory proteins are exported from the endoplasmic reticulum (ER) at specialized subcompartments called exit sites (ERES). Cargoes like procollagen are too large for export by the standard COPII- coated vesicle of 60 nm average diameter. We have previously suggested that procollagen is transported from the ER to the next secretory organelle, the ER-Golgi intermediate compartment (ERGIC), in TANGO1- dependent interorganelle tunnels. In the theoretical model presented here, we suggest that intrinsically disordered domains of TANGO1 in the ER lumen induce an entropic contraction, which exerts a force that draws procollagen toward the ERES. Within this framework, molecular gradients of pH and/or HSP47 between the ER and ERGIC create a force in the order of tens of femto- Newtons. This force is substantial enough to propel procollagen from the ER at a speed of approximately 1 nm center dot s-1. This calculated speed and the quantities of collagen secreted are similar to its observed physiological secretion rate in fibroblasts, consistent with the proposal that ER export is the rate- limiting step for procollagen secretion. Hence, the mechanism we propose is theoretically adequate to explain how cells can utilize molecular gradients and export procollagens at a rate commensurate with physiological needs.