New insights into the hemolymph coagulation cascade of horseshoe crabs initiated by autocatalytic activation of a lipopolysaccharide-sensitive zymogen.

The concept of a chain reaction of proteolytic activation of multiple protease zymogens was first proposed to explain the blood clotting system in mammals as an enzyme cascade. In multicellular organisms, similar enzyme cascades are widely present in signal transduction and amplification systems. The initiation step of the blood coagulation cascade often consists of autocatalytic activation of the corresponding zymogens located on the surfaces of host- or foreign-derived substances at injured sites. However, the molecular mechanism underlying the concept of autocatalytic activation remains speculative. In this review, we will focus on the autocatalytic activation of prochelicerase C on the surface of lipopolysaccharide as a potential initiator of hemolymph coagulation in horseshoe crabs. Prochelicerase C is presumed to have evolved from a common complement factor in Chelicerata; thus, evolutionary insights into the hemolymph coagulation and complement systems in horseshoe crabs will also be discussed.