title: Multienzyme degradation of host serum albumin in ticks.
abstract: Host blood proteins, represented mainly by hemoglobin and serum albumin, serve as the ultimate source of amino acids needed for de novo protein synthesis during tick development and reproduction. While uptake and processing of hemoglobin by tick gut cells have been studied in detail, molecular mechanisms of host serum albumin degradation remain unknown. In this work, we have used artificial membrane feeding of Ixodes ricinus females on a hemoglobin-free diet in order to characterize the proteolytic machinery involved in albuminolysis. Morphological comparisons of ticks fed on whole blood (BF) and serum (SF) at microscopic and ultrastructural levels showed that albumin and hemoglobin have different trafficking routes in tick gut cells. Analysis in vitro with selective inhibitors demonstrated that albumin is degraded at an acidic pH by a network of cysteine and aspartic peptidases with predominant involvement of cysteine cathepsins having endo- and exopeptidase activities. The cleavage map of albumin and the roles of individual peptidases in albumin degradation were determined. These results indicate that the albuminolytic pathway is controlled by the same proteolytic system that is responsible for hemoglobinolysis. This was further supported by the overall similarity of gut peptidase profiles in SF and BF ticks at the transcriptional and enzymatic activity levels. In conclusion, our work provides evidence that although hemoglobin and albumin are transported differentially during heterophagy they are digested by a common multienzyme proteolytic network. This central digestive system, critical for successful blood feeding in tick females, thus represents a valuable target for novel anti-tick interventions.
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic. Electronic address: sojkadan@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sojka
authors.affiliation: Institute of Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, 166 10 Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Pytelková
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic; Faculty of Science, University of South Bohemia, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Perner
authors.affiliation: Institute of Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, 166 10 Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Horn
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic; Faculty of Science, University of South Bohemia, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Konvičková
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic; Faculty of Science, University of South Bohemia, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Schrenková
authors.affiliation: Institute of Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, 166 10 Prague, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Mareš
authors.affiliation: Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, 373 11 Ceske Budejovice, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kopáček
mesh_terms: D000818:Animals; D057055:Aspartic Acid Proteases / Q000378:metabolism*; D057056:Cysteine Proteases / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D018884:Ixodes / Q000201:enzymology*; D059748:Proteolysis; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D012709:Serum Albumin; D057055:Aspartic Acid Proteases; D057056:Cysteine Proteases
keywords: Albumin digestion; Gut; Proteolysis; Tick