Our lab is working on the structure-function relationship of the integrin receptors, in particular Beta2, AlphavBeta3, and AlphaIIbBeta3 integrins.

José Luis Alonso, PhD 
Instructor of Medicine/ Assistant in Biology 
149 13th Street
Charlestown, MA 02129
Phone: (617) 726-5664
Fax: (617) 726-5669
Email: jalonso@partners.org

 

A. Structure-activity relationships in integrins. Our lab is working on the structure-function relationship of the integrin receptors, in particular Beta2, AlphavBeta3, and AlphaIIbBeta3 integrins. They are expressed on the cell surface in an inactive state, thereby preventing cells from inappropriately adhering to each other or to the ECM unless activated by a physiologic stimulus (inside-out signaling). Then, integrins undergo rapid and reversible conformational-dependent changes in affinity, and avidity. Binding of ligand and/or application of external mechanical forces causes further changes in integrin conformation, and this change transduces an outside-in signal to the cell interior. We are testing specific, structure-based hypothesis for integrin activation and signaling.  We are also developing novel techniques for fluorescent analysis of integrins and to probe activation induced conformational changes in integrins on live cells.

B. Mechanochemical signaling in podocytes. The goal of this project is to study the molecular basis of cellular mechano-chemical signaling and cell mechanical behavior in renal podocytes. We address these questions using magnetic tweezers, cell stretching, traction microscopy, intracellular stress tomography, and spontaneous bead motion. This work is carried out in collaboration with the Biophysics Dept. of the University of Erlangen-Nuremberg.

 

References:
  1. Goldmann WH, Alonso JL, et al. Cell Shape Control and Mechanical Signalling through the Cytoskeleton. In: Carraway KL, Carraway CAC, editors. Cytoskeleton: Signaling and Cell Regulation. A Practical Approach. Oxford, England: Oxford University Press; 2000. p. 245-76.
  2. Alonso JL, Essafi M, Xiong J-P, Stehle T, Arnaout MA. Does the integrin alphaA Domain Act as a Ligand for its betaA Domain? Curr. Biol. 2002; 12: R340-2.
  3. Alonso JL, Goldmann WH. Feeling the Forces: Atomic Force Microscopy in Cell Biology. Life Sciences. 2003; 72: 2553-60.
  4. Chen CS, Alonso JL, Ostuni E, Whitesides GM, Ingber DE. Cell Shape provides Global Control of Focal Adhesion Assembly. Biochem Biophys Res Commun. 2003; 307: 355-61.
  5. Gupta V, Gylling A, Alonso JL, Sugimori T, Ianakiev P, Xiong J-P, Arnaout MA. The beta-tail domain (betaTD) regulates physiologic ligand binding to integrin CD11b/CD18. Blood. 2007; 109: 3513-3520.
  6. Alonso JL*, Gupta V*, Sugimori T, Essafi M, Xiong J-P, Arnaout MA. Role of the beta-Subunit Arginine/Lysine finger in Integrin Heterodimer Formation and Function. J. Immunol. 2008; 108: 1713-1718.
  7. Klemm AH, Diez G, Alonso JL, Goldmann WH. Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts. Biochem. Biophys. Res. Commun. 2009; 379: 799-801.
  8. Xiong J-P, Mahalingham B, Alonso JL, Borrelli LA, Rui X, Anand S, Hyman BT, Rysiok T, Muller-Pompalla D, Goodman SL, Arnaout MA. Crystal Structure of the complete  alphaVbeta3 Ectodomain plus an a/b Transmembrane Fragment. J Cell Biol. 2009; 186: 589-600.