Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs

J Cell Biol. 2020 Aug 3;219(8):e201907058. doi: 10.1083/jcb.201907058.

Abstract

Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Movement
  • Extracellular Matrix / enzymology*
  • Extracellular Matrix / pathology
  • Female
  • Gelatin / metabolism
  • Golgi Apparatus / enzymology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Macrophages / enzymology*
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Nucleobindins / genetics
  • Nucleobindins / metabolism*
  • Protein Transport
  • Proteolysis
  • Time Factors

Substances

  • NUCB1 protein, human
  • Nucleobindins
  • Gelatin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP14 protein, human
  • Matrix Metalloproteinase 14
  • Calcium