Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei

Biochemistry. 1993 Apr 13;32(14):3737-42. doi: 10.1021/bi00065a028.

Abstract

The surface of the bloodstream forms of Trypanosoma brucei is covered by the abundant glycosylphosphatidylinositol-anchored variant surface protein (mfVSG). During differentiation of bloodstream forms to the insect-stage or procyclic forms, the mfVSG is replaced by another glycoprotein, designated procyclic acidic repetitive protein (PARP) or procyclin. Shortly after differentiation is triggered in vitro, a cell-associated fragment of mfVSG can be detected which is subsequently released into the culture medium. In the case of the mfVSG of the variant clone MITat 1.4 (470 amino acid residues), fragmentation occurs close to the COOH-terminus (Gln433 or Thr434) as shown by NH2-terminal sequencing, metabolic labeling experiments, and molecular weight determinations by laser desorption/ionization mass spectrometry. Two invariant surface glycoproteins, which are anchored in the membrane by hydrophobic sequences close to their COOH-termini, are lost from the surface with similar kinetics as mfVSG. The data suggest that trypanosomes synthesize or activate a developmentally-regulated proteinase which degrades the glycoproteins at the surface, at the membrane lining the flagellar pocket, and/or in an early endocytic compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Endopeptidases / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protease Inhibitors / pharmacology
  • Protozoan Proteins*
  • Trypanosoma brucei brucei / growth & development*
  • Trypanosoma brucei brucei / metabolism
  • Variant Surface Glycoproteins, Trypanosoma / chemistry
  • Variant Surface Glycoproteins, Trypanosoma / metabolism*

Substances

  • Membrane Glycoproteins
  • Peptide Fragments
  • Protease Inhibitors
  • Protozoan Proteins
  • Variant Surface Glycoproteins, Trypanosoma
  • procyclic acidic repetitive protein, Trypanosoma
  • Endopeptidases