Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis

Journal of Thrombosis and Haemostasis : JTH
Tomoyuki SasakiKatsue Suzuki-Inoue

Abstract

Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [W...Continue Reading

References

Oct 8, 1999·Biochemical and Biophysical Research Communications·C H ChungT F Huang
Nov 30, 2006·The Journal of Biological Chemistry·Aleksandra A WatsonChristopher A O'Callaghan
Jul 10, 2007·The Journal of Biological Chemistry·Katsue Suzuki-InoueYukio Ozaki
Jan 25, 2008·The Biochemical Journal·Charita M ChristouChris A O'Callaghan
Jun 28, 2008·Protein Science : a Publication of the Protein Society·Aleksandra A WatsonChris A O'Callaghan
Oct 23, 2008·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Takashi Tsuruo, Naoya Fujita
Mar 31, 2010·Toxicon : Official Journal of the International Society on Toxinology·Kenneth J Clemetson
Jan 25, 2011·Nature Reviews. Cancer·Laurie J Gay, Brunhilde Felding-Habermann
Dec 24, 2011·Applied and Environmental Microbiology·Chun YouY-H Percival Zhang
Sep 11, 2014·Molecular & Cellular Proteomics : MCP·Marlis ZeilerMatthias Mann
Sep 12, 2015·International Journal of Cancer. Journal International Du Cancer·Nailin Li
May 8, 2016·Blood·Raphael Leblanc, Olivier Peyruchaud
Dec 29, 2016·Journal of Thrombosis and Haemostasis : JTH·T ShiraiK Suzuki-Inoue

❮ Previous
Next ❯

Citations

Jun 5, 2018·Platelets·Katsue Suzuki-Inoue
Mar 18, 2020·Journal of Clinical Medicine·Marie-Christine AlessiBernard Payrastre
Jun 2, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jiro IchikawaHirotaka Haro
Jan 3, 2019·The Journal of Clinical Investigation·Julie RayesBernhard Nieswandt
Mar 29, 2021·Journal of Thrombosis and Haemostasis : JTH·Shimon OtakeKatsue Suzuki-Inoue
May 4, 2021·Frontiers in Cell and Developmental Biology·Wolfgang M J ObermannJohannes A Eble
Jul 30, 2021·Frontiers in Oncology·Attila BraunElmina Mammadova-Bach

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.