news
Shrimp study exposes mechanisms of innate immunity
involve a concerted program of actin polymerization and depolymerization, myosin-based actin microfilament contraction, For most life on earth, defense against and finally phagosome digestion. pathogenic infection is not a matter of Short-interfering RNAs (siRNAs) diB cells and T cells, but rather of innate rected against PjRan diminished WSSV immunity. Now researchers have idenphagocytosis in shrimp hemolymph tified a novel player in driving that re(the invertebrate analog of blood) by sponse. Xiaobo Zhang and colleagues RNA interference, whereas excess Pjat Zhejiang University, Xiamen UniverRan mRNA increased phagocytosis. sity, the State Oceanic Administration, Similarly, PjRan mRNA and and Jimei University (all in siRNA decreased and inChina) write in JPR (DOI creased WSSV titers in shrimp 10.1021/pr800840x) that the hemolymph, respectively, small G protein, Ran GTPase, “suggesting that the Ran GTplays a key role in phagocytoPase participated in the antisis and antiviral immunity in viral immunity by regulating shrimp, a model invertebrate. phagocytosis,” Zhang says. The observation, says Zhang and his team specuZhang, was unexpected. Prelate that PjRan could regulate viously, Ran proteins were phagocytosis through its inassociated with nucleocytoteraction with myosin, possiplasmic transport and assembly by controlling the motor’s bly of the mitotic spindle, ATPase cycle (and thus, its nuclear envelope, and New role for Ran. With several analytical techniques, scientists contractile activity). Future nucleus. But phagocytosis is uncover evidence that Ran GTPases are involved in innate immunity in studies will be conducted to a cytoplasmic event. “Our shrimp. investigate this idea, he says. study revealed a completely Other future work will focus novel aspect of Ran GTPase on characterizing the in phagocytosis by the direct Ran-myosin-actin complex, identify“Penaeid shrimp culture is a worldwide interaction with the cytoskeleton proing the protein domains that hold the economic activity especially important for tein and presented a novel pathway complex together, and studying how intertropical developed and developing concerning antiviral immunity,” he the complex interfaces with WSSV countries,” says Zhang. “However, the inpoints out. itself. tensification of shrimp farming has been Unlike more complex vertebrates, Innate immunity may be a key factor accompanied by the development of whose immune systems depend for invertebrate antipathogen defenses, many infectious diseases, especially from heavily (though not exclusively) on but it is not limited to those organviral origin, which cause a decrease in adaptive, antigen-specific responses isms. Vertebrates, too, use innate growth in shrimp production resulting in such as antibodies and T cell receptors, mechanisms; macrophages and denvast economic losses.” invertebrate defenses use generic, indritic cells, for instance, use phagPreviously, Zhang and his team had nate immunity, which typically entails ocytosis to eliminate pathogens in hunoted a link between P. japonicus Ran the internalization (phagocytosis) and mans. How much the present study GTPase (PjRan) expression and WSSV redigestion of potential pathogens. The will illuminate these processes remains sistance, with the enzyme “significantly process involves mobilization of the to be seen. up-regulated in WSSV-resistant shrimp as cell cytoskeleton and requires several Concludes Zhang, “Our study will well as in WSSV-infected shrimp; [this sugclasses of small G proteins. [help us] better understand the mechagests] that the PjRan might be implicated G proteins are molecular switches, nism of shrimp antiviral immunity and in the innate immune system against virus proteins whose activity is governed by contribute to the further compreheninfection,” says Zhang. the particular form of guanosine nuclesion of antiviral signal pathways in inIn the current study, Zhang’s group inotide cofactor to which they are vertebrates.” vestigated PjRan’s binding partners. With bound. The inactive form of the pro—Jeffrey M. Perkel coimmunoprecipitation, sequencing by tein is associated with GDP; when that MS, and immunoelectron microscopy, the protein swaps out GDP for GTP, it team found that PjRan associates and coswitches on and remains on until the localizes with myosin light chain, an actinprotein’s intrinsic GTPase hydrolyzes associated molecular motor, which is inthe GTP back to GDP. volved in phagocytosis. Indeed, myosin Small G proteins come in several forms, activity drives phagocytic processes, which including the Rho and Rab families, both XIAOBO ZHANG
of which have previously been implicated in phagocytosis. One class of G proteins that was not known to play a role in innate immunity was the Ran GTPases. Now Zhang and his colleagues have filled that gap and demonstrated that in Penaeus japonicus (penaeid shrimp), the Ran GTPase is required to protect the organisms from infection with white spot syndrome virus (WSSV).
10.1021/pr8010777
© 2009 American Chemical Society
Journal of Proteome Research • Vol. 8, No. 3, 2009 1107
