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The role of lipid microdomains in signaling and cytoskeletal reorganization in migrating leukocytes and tumor cells

English title The role of lipid microdomains in signaling and cytoskeletal reorganization in migrating leukocytes and tumor cells
Applicant Niggli Sigel Verena
Number 103708
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pathologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cellular Biology, Cytology
Start/End 01.04.2004 - 31.03.2009
Approved amount 188'442.00
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Keywords (4)

RhoA; Rac; cell signaling; cell motility

Lay Summary (English)

Lay summary
1. Aims of the project:
Our research is focused on the elucidation of themolecular mechanisms of cell migration. Directed migration of cellsdepends on the interaction of chemotactic molecules with their specificreceptors. This results in localized signaling which inducesreorganization of the cytoskeleton, changes in cell shape and celladhesion, events crucial for cell locomotion. Many aspects of localsignalling are incompletely characterized. Lipid microdomains (rafts) inthe plasma membrane represent a central feature of cellular organizationwhich could be crucial for the local activation of specific signalingcascades. As model systems for analysis of cell migration we use therapidly migrating human neutrophils, neutrophil-like HL-60 cells and a rattumor cell line. The experiments should lead to information on whetherimportant signaling molecules are located in or excluded from rafts, toinformation on the impact of cell activation on raft composition and onthe role of rafts in localizing and regulating specific signalingmolecules in specific areas of polarized neutrophils and Walkercarcinosarcoma cells. We will focus especially on small GTP-bindingproteins of the Rho family, on the enzyme phospatidylinositol 3-kinase andits product phosphatidylinositol 3,4,5-trisphosphate.

2. Significance of the project:
We expect that the obtained knowledgeprovides novel information on the role of lipid rafts in coordinatingsignaling for cell migration in neutrophils and a tumor cell line. Thisshould be important for our understanding of the mechanisms of neutrophiland tumor cell motility, processes involved in inflammation and tumormetastasis.

3. Scientific backgraound and methodology:
Directed cell locomotion is crucial for physiological processes such asembryonal development and host defense against pathogens and plays also animportant role in pathological events such as neoplastic invasion. Theelucidation of molecular mechanisms of cell migration in specific celltypes is important for our understanding of these processes.
We plan to use the following methods: Cell migration will be assessed byvideo microscopy. Raft composition of neutrophils, neutrophil-like HL-60cells and Walker carcinosarcoma cells will be analyzed using biochemicaltechniques (fractionation of cell lysates obtained by extracting cellswith different detergents preserving different types of rafts on sucrosedensity gradients, followed by immunoblotting of the fractions). Raftswill also be visualized in living motile cells and in fixed cells usingfluorescence labeling techniques and immunofluorescence microscopy.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
129655 The role of specific membrane microdomain components (flotillins) in signaling, cytoskeletal reorganization, adhesion and migration of leukocytes and tumor cells 01.05.2010 Project funding (Div. I-III)
58836 Signalling for cell locomotion and cytoskeletal reorganization inleukocytes and tumor cells 01.10.2000 Project funding (Div. I-III)