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2007 Scientific Report

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VARI | 2007 Surprisingly, DIP had no effect on the highly related mDia1. Consistent with a role for mDia2 as a Cdc42 effector, DIP both blocked the formation of filopodia and induced non-apoptotic membrane blebbing, a physiological process involved in both cytokinesis and amoeboid cell movement. DIP-induced blebbing occurred independently of Arp2/3 activity. Figure 3 shows the result of microinjection of DIP LRR into a mouse embryo fibroblast in which a critical subunit of Arp2/3 has been knocked down by siRNA. The experiment reveals a pivotal role for DIP in the control of nonbranched versus branched actin filament assembly mediated, respectively, by Diaphanous-related formins and by activators of Arp2/3. The ability of DIP to trigger blebbing also suggests a role for mDia2 in the assembly of actin filaments at the cell cortex necessary for the maintenance of plasma membrane integrity. Future experiments will address how DIP regulates mDia2 in directed cell movement and during cell division. Figure 3. Figure 3. DIP LRR–induced plasma membrane blebbing does not require Arp2/3 activity. This mouse embryo fibroblast, which expresses siRNA directed against Arp3, was injected with 0.1 μM recombinant DIP LRR protein along with Texas Red dextran as a marker. 9 External Collaborators Harry Higgs, Dartmouth Medical School, Hanover, New Hampshire Recent Publications From left: Peng, Holman, DeWard, Eisenmann, Kitchen, Alberts, Hildebrand Eisenmann, Kathryn M., Elizabeth S. Harris, Susan M. Kitchen, Holly A. Holman, Henry N. Higgs, and Arthur S. Alberts. 2007. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Current Biology 17(7): 579–591. Wallar, Bradley J., Aaron D. DeWard, James H. Resau, and Arthur S. Alberts. 2007. RhoB and the mammalian Diaphanousrelated formin mDia2 in endosome trafficking. Experimental Cell Research 313(3): 560–571.

Van Andel Research Institute | Scientific Report Brian Cao, M.D. Laboratory of Antibody Technology 10 Dr. Cao obtained his M.D. from Peking University Medical Center, People’s Republic of China, in 1986. On receiving a CDC fellowship award, he was a visiting scientist at the National Center for Infectious Diseases, Centers for Disease Control and Prevention in Atlanta (1991–1994). He next served as a postdoctoral fellow at Harvard (1994–1995) and at Yale (1995–1996). From 1996 to 1999, Dr. Cao was a Scientist Associate in charge of the Monoclonal Antibody Production Laboratory at the Advanced BioScience Laboratories–Basic Research Program at the National Cancer Institute, Frederick Cancer Research and Development Center, Maryland. Dr. Cao joined VARI as a Special Program Investigator in June 1999, and he was promoted to Senior Scientific Investigator in July 2006. Staff Laboratory Staff Ping Zhao, M.S. Tessa Grabinski, B.S. Students Students Xin Wang Ning Xu Aixia Zhang Jin Zhu Visiting Scientists

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