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    Last Name

    Elizabeth J Luna PhD

    TitleProfessor Emeritus
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    377 Plantation Street
    Worcester MA 01605
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCancer Center

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Cell Dynamics


        Cell and Developmental Biology Department

        Academic Background

        B.A., Chemistry, Southern Illinois University at Carbondale. 1972
        Ph.D., Physical Chemistry, Stanford University, 1977.
        NIH postdoctoral fellow, Cell and Molecular Biology, The Biological Laboratories,Harvard University, 1977-81
        Princeton University, Biology Department, 1981-88
        The Worcester Foundation for Experimental Biology, 1988-97
        University of Massachusetts Medical School,1989-present


        Membrane Skeleton Dynamics, Motility, Adhesion, Signal Transduction

        As cells move, internal movements caused by their actin and microtubule cytoskeletons must be coordinated with events at their plasma membranes. During the cycle of events associated with cell translocation, the cells extend surface protrusions at their leading edges, make contact with the substratum at focal adhesions, and then disassemble the focal adhesions in the rear of the cell as the cell retracts its posterior to provide material for another round of surface protrusion. A lot is known about individual steps in this cycle, but much less is known about how the different steps are coordinated at the interface between the membrane and the cytoskeleton, a region of the cell known as the "membrane skeleton".

        Our laboratory is interested in how the membrane skeleton controls the component events during very rapid cell movement, how it regulates cellular processes, such as chemotaxis and matrix invasion, and how these proteins are involved in organism-scale motile phenomena, including wound healing and immune function. Most of the same or similar proteins that we found in membrane skeletons from neutrophils (a type of white blood cell) also exist in human cervical and breast carcinoma cell lines and in smooth and striated muscle membranes. These proteins include cytoskeletal proteins (spectrin, actin, myosins I and II,a -actinin, supervillin), signaling proteins (Src family kinases, heterotrimeric G proteins), and proteins that organize cholesterol-enriched membrane domains (stomatin, flotillins).

        Of these membrane skeleton proteins, supervillin is of special interest to us. Supervillin binds tightly to the neutrophil plasma membrane and also binds directly to at least six different cytoskeletal proteins, including actin- and microtubule-associated motors. Additional candidate supervillin interaction partners include a large number of oncogenes, tumor suppressors, and other proteins implicated in motile processes. Over- and under-expression of supervillin affects each step of the motility cycle. The gene encoding supervillin maps to a region of human chromosome 10p implicated in tumor cell motility and susceptibility to obesity and diabetes. Taken together, the working hypothesis is that supervillin is a membrane-associated adapter protein that works with a group of interacting proteins to regulate rapid motility and associated signaling processes in many cell types.

        The supervillin-associated membrane skeleton localizes to specialized membrane structures, called podosomes in tissue culture cells and costameres in striated muscle. Targeting of supervillin structures to cell-substrate contact sites called focal adhesions results in focal adhesion disassembly. Reduced levels of supervillin disrupt the stimulus-mediated activation of the ERK1/2 family of mitogen-activated kinases, suggesting an important signaling role at either the plasma membrane or at internal sites of ERK1/2 activation. Live cell imaging of EGFP-tagged supervillin is consistent with associations with internal trafficking membranes, as well as at the plasma membrane.

        Current projects include exploring the biochemical basis for supervillin-mediated activation of myosin contractility, identifying the mechanism(s) by which supervillin promotes reorganization of the actin cytoskeleton during invasion of extracellular matrices, and characterization of the role of the supervillin cytoskeleton during endosomal trafficking. We also have generated a supervillin-deficient mouse for studies of organ function; initial experiments on muscle contractility, immune function, and wound healing are in progress. The overall working hypothesis is that the supervillin-associated membrane skeleton coordinates cell motility and matrix invasion by promoting protein activation and trafficking at several steps in the motility cycle. The long-term goal is to understand how this coordination works during the motility and invasion associated with immune function, cancer metastasis, embryogenesis, and the formation of new blood vessels.


        Figure 1: The intracellular localization of supervillin in MDBK cells is a function of cell density and adherence state. In subconfluent cells (left), supervillin (red) is found in the nucleus, in the cytoplasm, and in spots along the plasma membrane with the cell adhesion protein, E-cadherin (green). In confluent cells (right), supervillin and E-cadherin co-localize almost completely (yellow) at sites of lateral cell-cell contact.


        Luna Figure 2

        Figure 2: Working model of the neutrophil membrane skeleton. Supervillin is the most cytoskeletal protein that is the most proximal to the membrane bilayer, followed by myosins I and II (Nebl et al., 2002).


        Movie: EGFP-supervillin in COS7 cells localizes with dynamic structures at and near the cell periphery. Some of these structures are peripheral bundles of membrane-associated actin and myosin II; other EGFP-supervillin localizations appear to be trafficking endosomal membranes.

        Rotation Projects

        Potential Rotation Projects

        Rotation projects involving biochemical, molecular genetic, and/or cell-based techniques can be tailored to the interests of the students. Questions associated with ongoing projects described above in the Research section are available for students who want to learn a specific technique. Questions relevant to the laboratory’s interests that could be developed into independent thesis projects include:

        1. Medium throughput functional screens of supervillin-associated proteins to determine which influence motility, adhesion, contractility, or the formation and function of matrix-invading structures called invadopodia;
        2. Analysis of motile and signaling dysfunctions in cells and tissues from mice deficient in expression of supervillin isoforms; and
        3. Function of these membrane skeleton proteins during ‘nongenomic’, plasma membrane-based, responses to steroid receptors in breast or prostate cancer cells.

        selected publications
        List All   |   Timeline
        1. Pollock LM, Gupta N, Chen X, Luna EJ, McDermott BM. Supervillin Is a Component of the Hair Cell's Cuticular Plate and the Head Plates of Organ of Corti Supporting Cells. PLoS One. 2016; 11(7):e0158349.
          View in: PubMed
        2. Son K, Smith TC, Luna EJ. Supervillin binds the Rac/Rho-GEF Trio and increases Trio-mediated Rac1 activation. Cytoskeleton (Hoboken). 2015 Jan; 72(1):47-64.
          View in: PubMed
        3. Spinazzola JM, Smith TC, Liu M, Luna EJ, Barton ER. Gamma-sarcoglycan is required for the response of archvillin to mechanical stimulation in skeletal muscle. Hum Mol Genet. 2015 May 1; 24(9):2470-81.
          View in: PubMed
        4. Lawlor MW, Viola MG, Meng H, Edelstein RV, Liu F, Yan K, Luna EJ, Lerch-Gaggl A, Hoffmann RG, Pierson CR, Buj-Bello A, Lachey JL, Pearsall S, Yang L, Hillard CJ, Beggs AH. Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice. Am J Pathol. 2014 Jun; 184(6):1831-42.
          View in: PubMed
        5. Smith TC, Fridy PC, Li Y, Basil S, Arjun S, Friesen RM, Leszyk J, Chait BT, Rout MP, Luna EJ. Supervillin binding to myosin II and synergism with anillin are required for cytokinesis. Mol Biol Cell. 2013 Dec; 24(23):3603-19.
          View in: PubMed
        6. Fang Z, Luna EJ. Supervillin-mediated suppression of p53 protein enhances cell survival. J Biol Chem. 2013 Mar 15; 288(11):7918-29.
          View in: PubMed
        7. Fedechkin SO, Brockerman J, Luna EJ, Lobanov MY, Galzitskaya OV, Smirnov SL. An N-terminal, 830 residues intrinsically disordered region of the cytoskeleton-regulatory protein supervillin contains Myosin II- and F-actin-binding sites. J Biomol Struct Dyn. 2013 Oct; 31(10):1150-9.
          View in: PubMed
        8. Edelstein LC, Luna EJ, Gibson IB, Bray M, Jin Y, Kondkar A, Nagalla S, Hadjout-Rabi N, Smith TC, Covarrubias D, Jones SN, Ahmad F, Stolla M, Kong X, Fang Z, Bergmeier W, Shaw C, Leal SM, Bray PF. Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress. Circulation. 2012 Jun 5; 125(22):2762-71.
          View in: PubMed
        9. Bhuwania R, Cornfine S, Fang Z, Kr├╝ger M, Luna EJ, Linder S. Supervillin couples myosin-dependent contractility to podosomes and enables their turnover. J Cell Sci. 2012 May 1; 125(Pt 9):2300-14.
          View in: PubMed
        10. Smith TC, Fang Z, Luna EJ. Novel interactors and a role for supervillin in early cytokinesis. Cytoskeleton (Hoboken). 2010 Jun; 67(6):346-64.
          View in: PubMed
        11. Fang Z, Takizawa N, Wilson KA, Smith TC, Delprato A, Davidson MW, Lambright DG, Luna EJ. The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility. Traffic. 2010 Jun; 11(6):782-99.
          View in: PubMed
        12. Crowley JL, Smith TC, Fang Z, Takizawa N, Luna EJ. Supervillin reorganizes the actin cytoskeleton and increases invadopodial efficiency. Mol Biol Cell. 2009 Feb; 20(3):948-62.
          View in: PubMed
        13. Takizawa N, Ikebe R, Ikebe M, Luna EJ. Supervillin slows cell spreading by facilitating myosin II activation at the cell periphery. J Cell Sci. 2007 Nov 1; 120(Pt 21):3792-803.
          View in: PubMed
        14. Takizawa N, Smith TC, Nebl T, Crowley JL, Palmieri SJ, Lifshitz LM, Ehrhardt AG, Hoffman LM, Beckerle MC, Luna EJ. Supervillin modulation of focal adhesions involving TRIP6/ZRP-1. J Cell Biol. 2006 Jul 31; 174(3):447-58.
          View in: PubMed
        15. Peterman TK, Ohol YM, McReynolds LJ, Luna EJ. Patellin1, a novel Sec14-like protein, localizes to the cell plate and binds phosphoinositides. Plant Physiol. 2004 Oct; 136(2):3080-94; discussion 3001-2.
          View in: PubMed
        16. Gangopadhyay SS, Takizawa N, Gallant C, Barber AL, Je HD, Smith TC, Luna EJ, Morgan KG. Smooth muscle archvillin: a novel regulator of signaling and contractility in vascular smooth muscle. J Cell Sci. 2004 Oct 1; 117(Pt 21):5043-57.
          View in: PubMed
        17. Chen Y, Takizawa N, Crowley JL, Oh SW, Gatto CL, Kambara T, Sato O, Li XD, Ikebe M, Luna EJ. F-actin and myosin II binding domains in supervillin. J Biol Chem. 2003 Nov 14; 278(46):46094-106.
          View in: PubMed
        18. Oh SW, Pope RK, Smith KP, Crowley JL, Nebl T, Lawrence JB, Luna EJ. Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton. J Cell Sci. 2003 Jun 1; 116(Pt 11):2261-75.
          View in: PubMed
        19. Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, Luna EJ. Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem. 2002 Nov 8; 277(45):43399-409.
          View in: PubMed
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