Cell adhesion-induced transient interaction of ADAM15 with poly(A) binding protein at the cell membrane colocalizes with mRNA translation

PLoS One. 2018 Sep 28;13(9):e0203847. doi: 10.1371/journal.pone.0203847. eCollection 2018.

Abstract

The regulation of temporo-spatial compartmentalization of protein synthesis is of crucial importance for a variety of physiologic cellular functions. Here, we demonstrate that the cell membrane-anchored disintegrin metalloproteinase ADAM15, upregulated in a variety of aggressively growing tumor cells, in the hyperproliferative synovial membrane of inflamed joints as well as in osteoarthritic chondrocytes, transiently binds to poly(A) binding protein 1 (PABP) in cells undergoing adhesion. The cytoplasmic domain of ADAM15 was shown to selectively interact with the proline-rich linker of PABP. Immunostainings of adhesion-triggered cells demonstrate an ADAM15-dependent recruitment of PABP to cell membrane foci coinciding with ongoing mRNA translation as visualized by the detection of puromycin-terminated polypeptides. Moreover, the increase in cell membrane-associated neosynthesis of puromycylated proteins upon induction of cell adhesion was proven linked to ADAM15 expression in HeLa and ADAM15-transfected chondrocytic cells. Thus, down regulation of ADAM15 by siRNA and/or the use of a cell line transfected with a mutant ADAM15-construct lacking the cytoplasmic tail resulted in a considerable reduction in the amount of cell membrane-associated puromycylated proteins formed during induced cell adhesion. These results provide first direct evidence for a regulatory role of ADAM15 on mRNA translation at the cell membrane that transiently emerges in response to triggering cell adhesion and might have potential implications under pathologic conditions of matrix remodeling associated with ADAM15 upregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM Proteins / physiology*
  • Cell Adhesion / physiology*
  • Cell Communication
  • Cell Line
  • Cell Membrane / metabolism
  • Chondrocytes / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology*
  • Osteoarthritis / genetics
  • Osteoarthritis / physiopathology
  • Poly(A)-Binding Proteins / metabolism
  • Protein Biosynthesis / physiology
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology
  • Synovial Membrane / metabolism
  • Transfection

Substances

  • Membrane Proteins
  • Poly(A)-Binding Proteins
  • RNA, Messenger
  • ADAM Proteins
  • ADAM15 protein, human

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft DFG grant DFG BU 584/5-1.