title: Longistatin, a plasminogen activator, is key to the availability of blood-meals for ixodid ticks.
abstract: Ixodid ticks are notorious blood-sucking ectoparasites and are completely dependent on blood-meals from hosts. In addition to the direct severe effects on health and productivity, ixodid ticks transmit various deadly diseases to humans and animals. Unlike rapidly feeding vessel-feeder hematophagous insects, the hard ticks feed on hosts for a long time (5-10 days or more), making a large blood pool beneath the skin. Tick's salivary glands produce a vast array of bio-molecules that modulate their complex and persistent feeding processes. However, the specific molecule that functions in the development and maintenance of a blood pool is yet to be identified. Recently, we have reported on longistatin, a 17.8-kDa protein with two functional EF-hand Ca(++)-binding domains, from the salivary glands of the disease vector, Haemaphysalis longicornis, that has been shown to be linked to blood-feeding processes. Here, we show that longistatin plays vital roles in the formation of a blood pool and in the acquisition of blood-meals. Data clearly revealed that post-transcriptional silencing of the longistatin-specific gene disrupted ticks' unique ability to create a blood pool, and they consequently failed to feed and replete on blood-meals from hosts. Longistatin completely hydrolyzed α, β and γ chains of fibrinogen and delayed fibrin clot formation. Longistatin was able to bind with fibrin meshwork, and activated fibrin clot-bound plasminogen into its active form plasmin, as comparable to that of tissue-type plasminogen activator (t-PA), and induced lysis of fibrin clot and platelet-rich thrombi. Plasminogen activation potentiality of longistatin was increased up to 4 times by soluble fibrin. Taken together, our results suggest that longistatin may exert potent functions both as a plasminogen activator and as an anticoagulant in the complex scenario of blood pool formation; the latter is critical to the feeding success and survival of ixodid ticks.
authors.affiliation: Department of Global Agricultural Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.lastname: Anisuzzaman
authors.forename: M Khyrul
authors.initials: MK
authors.lastname: Islam
authors.forename: M Abdul
authors.initials: MA
authors.lastname: Alim
authors.forename: Takeharu
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hatta
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yamaji
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Kozo
authors.initials: K
authors.lastname: Fujisaki
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D001769:Blood; D002135:Calcium-Binding Proteins / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology*; D026863:Ixodidae / Q000502:physiology*; D010960:Plasminogen Activators / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012471:Salivary Proteins and Peptides / Q000502:physiology*
chemical_list: D000925:Anticoagulants; D002135:Calcium-Binding Proteins; D015800:Protozoan Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012471:Salivary Proteins and Peptides; C559189:longistatin protein, Haemaphysalis longicornis; D005337:Fibrin; D005340:Fibrinogen; D010960:Plasminogen Activators; D005341:Fibrinolysin