Laboratory of Cell Structure and Signal Integration

Scientific Overview

General Overview

Art Alberts’ laboratory is studying cell signaling and cell structure, in particular the structures that allow cells to change shape and to move. The ability of a cell to move is an essential aspect of a cancer cell’s ability to metastasize, i.e., to form tumors in the body distant from the original tumor. The family of proteins called Rho, which are active in signaling within cells and have an important role in the metastasis of cancer cells, are a major focus of the experiments. Also under study are the proteins called Diaphanous-related formins, molecules that can be activated by the Rho proteins and then create various changes in the molecular “skeleton” of actin filaments within the cell. Learning how these proteins combine to regulate a cell’s structures and functions is a major goal of the research.

Alberts, A.S. 2010. Formins: dangling plot threads in a multi-act performance. Biochim. Biophys. Acta 1803(2): 151.  PubMed    Article  

Deward, A.D., K.M. Eisenmann, S.F. Matheson, and A.S. Alberts. 2010. The role of formins in human disease. Biochim. Biophys. Acta 1803(2): 226–233.  PubMed    Article  

DeWard, A.D., and A.S. Alberts. 2009. Ubiquitin-mediated degradation of the formin mDia2 upon completion of cell division. J. Biol. Chem. 284(30): 20061-20069.  PubMed    Article  

DeWard, A.D., K. Leali, R. West, G.C. Prendergast, and A.S. Alberts. 2009. Loss of RhoB Expression Enhances the Myelodysplastic Phenotype of mammalian Diaphanous-related Formin mDia1 Knockout Mice. PLoS ONE 4(9): e7102.  PubMed    Article  

Eisenmann, K.M., K.J. Dykema, S.F. Matheson, N.F. Kent, A.D. DeWard, R.A. West, K.A. Furge, and A.S. Alberts. 2009. 5q- Myelodysplastic syndromes: chromosome 5q genes direct a tumor suppression network sensing actin dynamics. Oncogene 28(39): 3429-3441.  PubMed    Article  

Shi, Y., B. Dong, H. Miliotis, J. Liu, A.S. Alberts, J. Zhang, and K.A. Siminovitch. 2009. Src kinase Hck association with the WASp and mDia1 cytoskeletal regulators promotes chemoattractant-induced Hck membrane targeting and activation in neutrophils. Biochemistry and Cell Biology 87(1): 207-216.  PubMed    Article  

Shi, Y., J. Zhang, M. Mullin, B. Dong, A.S. Alberts, and K.A. Siminovitch. 2009. The mDial formin is required for neutrophil polarization, migration, and activation of the LARG/RhoA/ROCK signaling axis during chemotaxis. J. Immunol 182(6): 3837-3845.  PubMed    Article  

Deward, A.D., and A.S. Alberts. 2008. Microtubule stabilization: formins assert their independence. Current Biology 18(14): R605-R608.  PubMed    Article  

Sarmiento, C., W. Wang, A. Dovas, H. Yamaguchi, M. Sidani, M. El-Sibai, V. DesMarais, H.A. Holman, S. Kitchen, J.M. Backer, A. Alberts, and J. Condeelis. 2008. WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. J. Cell Biol. 180(6): 1245-1260.  PubMed    Article  

Wang, P., M.R. Bowl, S. Bender, J. Peng, L. Farber, J. Chen, A. Ali, Z. Zhang, A.S. Alberts, R.V. Thakker, A. Shilatifard, B.O. Williams, and B.T. Teh. 2008. Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice. Mol. Cell. Biol. 28(9): 2930-2940.  PubMed    Article  

Dent, E.W., A.V. Kwiatkowski, L.M. Mebane, U. Philippar, M. Barzik, D.A. Rubinson, S. Gupton, J.E. Van Veen, C. Furman, J. Zhang, A.S. Alberts, S. Mori, and F.B. Gertler. 2007. Filopodia are required for cortical neurite initiation. Nature Cell Biol. 9(12): 1347-1359.  PubMed    Article  

Eisenmann, K.M., E.S. Harris, S.M. Kitchen, H.A. Holman, H.N. Higgs, and A.S. Alberts. 2007. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr. Biol. 17(7): 579-591.  PubMed    Article  

Eisenmann, K.M., R.A. West, D. Hildebrand, S.M. Kitchen, J. Peng, R. Sigler, J. Zhang, K.A. Siminovitch, and A.S. Alberts. 2007. T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice. J. Biol. Chem. 282(34): 25152-25158.  PubMed    Article  

Gupton, S.L., K. Eisenmann, A.S. Alberts, and C.M. Waterman-Storer. 2007. mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. J. Cell Sci. 120(19): 3475-3487.  PubMed    Article  

Kamasani, U., J.B. DuHadaway, A.S. Alberts, and G.C. Prendergast. 2007. mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition. Cancer Biol. Therapy 6(9): 1422–1427.  PubMed    Article  

Peng, J., S.M. Kitchen, R.A. West, R. Sigler, K.M. Eisenmann, and A.S. Alberts. 2007. Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian Diaphanous–related formin mDia1. Cancer Res. 67(16): 7565-7571.  PubMed    Article    Featured in Nature  

Wallar, B.J., A.D. DeWard, J.H. Resau, and A.S. Alberts. 2007. RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking. Exp. Cell Res. 313(3): 560-571.  PubMed    Article  

Wallar, B.J., B.N. Stropich, J.A. Schoenherr, H.A. Holman, S.M. Kitchen, and A.S. Alberts. 2006. The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the Diaphanous-related formin inhibitory domain. J. Biol. Chem. 281(7): 4300–4307.  PubMed    Article  

Alberts, A.S., H. Qin, H.S. Carr, and J.A. Frost. 2005. PAK1 negatively regulates the activity of the Rho exchange factor NET1. J. Biol. Chem. 280(13): 12152–12161.  PubMed    Article  

Colucci-Guyon, Emma, Florence Niedergang, Bradley J. Wallar, Jun Peng, Arthur S. Alberts, and Philippe Chavrier. 2005. A role for mammalian Diaphanous-related formins in complement receptor (CR-3)-mediated phagocytosis in macrophages. Current Biology 15(22): 2007–2012.  PubMed    Article  

Eisenmann, Kathryn M., Jun Peng, Bradley J. Wallar, and Arthur S. Alberts. 2005. Rho GTPase-formin pairs in cytoskeletal remodeling. Signalling Networks in Cell Shape and Motility Novartis Foundation Symp. series, Vol. 269. London, U.K.: Novartis Foundation: 206–230.  PubMed  

Wen, Ying, Christina H. Eng, Jan Schmoranzer, Noemi Cabrera-Poch, Edward J.S. Morris, Michael Chen, Bradley J. Wallar, Arthur S. Alberts, and Gregg G. Gundersen. 2004. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nature Cell Biology 6(9): 820–830.  PubMed    Article  

Peng, Jun, Bradley J. Wallar, Akiko Flanders, Pamela J. Swiatek, and Arthur S. Alberts. 2003. Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Current Biology 13(7): 534-545.  PubMed    Article    Featured in Current Biology  

Wallar, Bradley J., and Arthur S. Alberts. 2003. The formins: active scaffolds that remodel the cytoskeleton. Trends in Cell Biology 13(8): 435-446.  PubMed    Article  

Alberts, Arthur S. 2002. Diaphanous-related Formin homology proteins. Current Biology 12(23): R796.  PubMed    Article  

Alberts, Arthur S. 2001. Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain. Journal of Biological Chemistry 276(4): 2824-2830.  PubMed    Article  

Tominaga, T., Sahai, E., Chardin, P., McCormick, F., Courtneidge, S.A., and Alberts, A.S. 2000. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Molecular Cell 5(1): 13-25.  PubMed    Article  

Alberts, A.S., Geneste, O., and Treisman, R. 1998. Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation. Cell 92(4): 475-487.  PubMed    Article  

Alberts, A.S., and Treisman, R. 1998. Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1. The EMBO Journal 17(14): 4075-4085.  PubMed    Article  

Sahai, E., Alberts, A.S., and Treisman, R. 1998. RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. The EMBO Journal 17(5): 1350-1361.  PubMed    Article  

Alberts, A.S., Arias, J., Brindle, P., Claret, F.X., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. 1994. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370(6486): 226-229.  PubMed    Article