Louise Cramer

LMCB, Department of Cell & Developmental Biology, UCL

Email: l.cramer@ucl.ac.uk

1987 - BSc (Hons)Imperial College, London
1991 - PhD Imperial College, London
1991 - Postdoctoral Fellow, University of California, San Francisco, Human Frontiers Science Programme fellowship
1994 - Senior Postdoctoral Fellow, University of California, San Francisco, American Cancer Society fellowship
1997 - career break/short scientist post, KCL
1998 - Group Leader, MRC-Laboratory Molecular Cell Biology, Royal Society University Research Fellow, and Dept. Cell and DevelopmentalBiology, UCL (2007-)
2002-2003 - career break
2005-2006 - career break
2003 - work part-time

Group Members

Tayamika Mseka, Tom Anderson

Past Group Members

Lyndall Briggs, Helen Dawe, Jody Rosenblatt, Karen McGee, Ashti Rampaul

Cytoskeleton Mechanisms in Cell Polarity and Cell Migration

Phase contrast movie of primary chick embryo heart fibroblasts migrating out from a tissue explant at about 1um/min.

Side-by-side movie of a migrating (left panel) and non-migrating (right panel) primary chick fibroblast. The migrating cell (left panel) has one cell front and one cell back and all parts of the cell move forward during directed migration (cell moves past the red circle). In contrast, in the non-migrating cell (right panel) there are multiple, delocalized protrusions and the cell does no net productive movement (no net movement past the red circle).

The crawling or gliding motion of adherent cells plays an important role in both normal animal physiology and disease. To migrate, cells must polarize their cell shape to form one cell front and one cell rear. In most animal cell types cell polarization and migration are powered by the actin cytoskeleton. In some cell types, microtubules also play an important role in polarizing cells. We study cytoskeleton mechanisms important for cell polarization and cell migration, mostly working with primary fibroblasts from chick embryo heart explants, a well established experimental model system. We focus on actin in the cell body and how distinct actin-based forces in the front and back of the cell coordinate during migration. We are also interested in how this is controlled by actin-binding proteins, and have discovered new roles for the actin depolymerization factor/cofilin (ADF/cofilin) family of proteins.

In contrast to actin in the leading cell edge, actin in the cell body has been very little studied in migrating cells, despite its importance for powering cell migration. Our work was the first to establish that organization of actomyosin II bundles (termed graded polarity actin bundles) in the cell body of migrating fibroblasts is distinct to the organization of stress fibres in non-migrating cells. Subsequently, graded polarity actin organization has also been identified in other migrating cell types by other labs, leading to new implications for both motile mechanism and regulation. We are currently determining how graded polarity actomyosin II bundles form during cell migration. The structural organization of actin required to establish the front and back of the cell remains surprisingly untested and we are also currently asking whether graded polarity organization in the cell body is important for driving the polarization of cells.

My lab, in collaboration with Prof. Jim Bamburg's lab at Colorado State University was the first to identify that actin depolymerization and the ADF/cofilin family of proteins is necessary for cell polarization in migrating fibroblasts. This was subsequently also discovered for several other migrating cell types by other labs, thus increasingly revealing the importance of these proteins for cell polarization in migrating cells. Our current endeavours focus on the molecular details controlling this pathway and we recently found a new role for ADF/cofilin in coordinating formation of the front and back of the cell. We found that ADF/cofilin controls the formation of oriented actomyosin II bundles in the cell body which in turn specifies the formation of the front and back of the cell around the ends of the bundles during cell polarization.

Given that our other work and that of other labs have also demonstrated the equally important role for actin depolymerization, actin severing and ADF/cofilin in leading edge protrusion, our longer term goal is to discover the spatial and temporal function of ADF and cofilin family members within the entire cell. How are the distinct types of actin organization within the front of the cell and cell body spatially and temporally controlled by ADF/cofilin during migration? We envisage answering this question will provide an understanding of how distinct actin force generating mechanisms are coordinated to overall power cell polarization and migration.

We are also interested in the role of the actin cytoskeleton in other types of cell motility and have discovered new roles for actomyosin II contraction in driving extrusion of apopotic cells, and in spindle assembly.

Selected Publications

Mseka, T., Coughlin, M., and L. P. Cramer 2009 Graded actin filament polarity is the organization of oriented actomyosin II filament bundles required for fibroblast polarization. Cell Motility Cytoskel 66: 743-753 DOI:10.1002/cm.20403.

Anderson, T. W., A. N. Vaughan and L. P. Cramer. 2008. Retrograde flow and myosin II activity within the leading cell edge deliver F-actin to the lamella to seed the formation of graded polarity actomyosin II filament bundles in migrating fibroblasts. Mol. Biol. Cell 19:5006-5018. doi: 10.1091

Cramer, L. P. 2008. Organelle motility: dynamic actin tracks for myosin motors. Current Biology 18: R1066-1086. doi: 10.1016

Mseka, T., Bamburg, J. R., and L. P. Cramer. 2007 . ADF/Cofilin mediates formation of oriented actin filament bundles in the cell body to trigger fibroblast polarization. J. Cell Science : 120: 4332-4344. DOI: 017640.

Rampaul, A., Parkin, I. P., and L. P. Cramer. 2007 . Damaging and protective properties of inorganic components of sunscreens applied to cultured human skin cells. J. Photochem. Photobiol. A: Chem 191:138-148 DOI:10.1016/j.jphotochem.2007.04.014

Zhang, J., Betson, M., Erasmus, J., Zeikos, K., Bailly, M., Cramer., L. P., and V. Braga. 2005 . Actin at cell-cell junctions is composed of two dynamic and functional populations. J. Cell Science 118: 5549-5562.

Rosenblatt, J., Cramer, L. P., Baum, B. and K. McGee, K. 2004 . Myosin-II dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly. Cell 117: 361-372

Dawe, H. R., Minamide, L. S., Bamburg, J. R., and L. P. Cramer. 2003 . ADF/Cofilin controls cell polarity during fibroblast migration. Current Biology 13:252-257.

Cramer, L. P. 2002 . Ena/Vasp: towards solving a cell motility paradox. Current Biology . 12:R417-419.

Cramer, L. P., Briggs, L., and H. R. Dawe. 2002 . Use of fluorescently labelled Deoxyribonuclease I to spatially measure G-actin levels in migrating and non-migrating cells. Cell Motility Cytoskel. 51: 27-38.

Rosenblatt, J., Martin C. Raff, M. C., and L. P. Cramer. 2001 . An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism . Current Biology , 11 : 23 :1847-1857.

Cramer, L. P. 2000 . Myosin VI: Roles for a minus-end directed actin motor in cells. J. Cell Biol 150: F121-126.

Cramer, L. P. 1999 . Role of actin filament disassembly in lamellipodium protrusion in motile cells revealed using the drug Jasplakinolide. Current Biology 9: 1095-1105.

Cramer, L. P. 1999 . Organization and polarity of actin filament networks in cells: implications for the mechanism of myosin-based cell motility. In Cell behaviour: control and mechanism of motility,. Eds: JM Lackie, GA Dunn, GE Jones Biochemical Society Symposium 65:173-206.


48 th ASCB annual meeting Dec 13-17 2008, San Francisco, CA.Co-chair, actin and actin binding proteins minisymposium: Louise Cramer	Editorial board: Louise Cramer	Front cover: Rosenblatt, J., Cramer, L. P., Baum, B. and K. McGee, K . 2004 . Cell 117: 361-372	Front cover: Rosenblatt, J., Martin C. Raff, M. C., and L. P. Cramer. 2001 . Current Biology , 11 : 23 :1847-1857.