An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion

Leigh A. Baxt, Rosanna P. Baker, Upinder Singh, Sinisa Urban

Research output: Contribution to journalArticlepeer-review

Abstract

Rhomboid proteases are membrane-embedded enzymes conserved in all kingdoms of life, but their cellular functions across evolution are largely unknown. Prior work has uncovered a role for rhomboid enzymes in host cell invasion by malaria and related intracellular parasites, but this is unlikely to be a widespread function, even in pathogens, since rhomboid proteases are also conserved in unrelated protozoa that maintain an extracellular existence. We examined rhomboid function in Entamoeba histolytica, an extracellular, parasitic ameba that is second only to malaria in medical burden globally. Despite its large genome, E. histolytica encodes only one rhomboid (EhROM1) with residues necessary for protease activity. EhROM1 displayed atypical substrate specificity, being able to cleave Plasmodium adhesins but not the canonical substrate Drosophila Spitz. We searched for substrates encoded in the ameba genome and found EhROM1 was able to cleave a cell surface lectin specifically. In E. histolytica trophozoites, EhROM1 changed localization to vesicles during phagocytosis and to the posterior cap structure during surface receptor shedding for immune evasion, in both cases colocalizing with lectins. Collectively these results implicate rhomboid proteases for the first time in immune evasion and suggest that a common function of rhomboid enzymes in widely divergent protozoan pathogens is to break down adhesion proteins.

Original languageEnglish (US)
Pages (from-to)1636-1646
Number of pages11
JournalGenes and Development
Volume22
Issue number12
DOIs
StatePublished - Jun 15 2008

Keywords

  • Erythrophagocytosis
  • Immune evasion
  • Pathogenesis
  • Presenilin
  • Serine protease
  • Site-2 protease

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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