title: The Schistosoma mansoni protein Sm16/SmSLP/SmSPO-1 is a membrane-binding protein that lacks the proposed microtubule-regulatory activity.
abstract: Sm16/SmSLP/SPO-1 (Sm16) has been identified as a developmentally regulated protein that is released from specific glands of the Schistosoma mansoni parasite during skin penetration. Sm16 has been ascribed both anti-inflammatory activities and a functional similarity with the conserved cytosolic tubulin-binding protein stathmin/Op18. Here we used a cell line to confirm signal peptide-dependent secretion and to define the secreted form of Sm16 for production in E. coli. We present evidence from both in vitro experiments and studies on transfected human cells that refute any functional similarity with stathmin/Op18. Instead of an Op18-like activity, we found that targeting of Sm16 to the cytosol of human cells, which was achieved by ectopic expression of Sm16 lacking the signal peptide, results in a caspase-dependent apoptotic response. Interestingly, by analysis of recombinant preparations we found that the secreted form of Sm16 is a lipid bilayer-binding protein that efficiently binds to the surface of diverse cell types by a polyanion-independent mechanism, which results in uptake by endocytosis. While the significance of the pro-apoptotic activity exerted by cytosolic Sm16 remains unclear, the present findings on cell-surface-binding properties of Sm16 seems likely to be of functional relevance during skin penetration of the parasite.
authors.affiliation: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden. per.holmfeldt@molbiol.umu.se
authors.forename: Per
authors.initials: P
authors.lastname: Holmfeldt
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Brännström
authors.forename: Mikael E
authors.initials: ME
authors.lastname: Sellin
authors.forename: Bo
authors.initials: B
authors.lastname: Segerman
authors.forename: Sven R
authors.initials: SR
authors.lastname: Carlsson
authors.forename: Martin
authors.initials: M
authors.lastname: Gullberg
mesh_terms: D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D004926:Escherichia coli / Q000235:genetics; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D012550:Schistosoma mansoni / Q000378:metabolism*
chemical_list: D015801:Helminth Proteins; D008051:Lipid Bilayers; D011994:Recombinant Proteins; C411707:SM16 protein, Schistosoma mansoni