Elements in regulation of the microfilament system
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
This thesis deals with cell motility. The process of rapid actin polymerization in the lamellipodium of a migrating cell is responsible for its protrusion. Studies have been made on some of the elements behind this event and special interest has been focused on the protein tropomyosin. Muscle tropomyosin and its function in regulating muscle contraction, have been studied for decades, but there are also multiple tropomyosin isoforms in non-muscle cells, whose detailed function has not been revealed. Previous work at this department has shown an involvement of tropomyosin in the assembly of actin in vitro in the presence of gelsolin, and initial studies located tropomyosin to the lamellipodium of stimulated human fibroblasts. However, the general view is that tropomyosin is depleted from the advancing cell edge, observations noted in support of the current model of Arp2/3 dependent formation of actin filaments in lamellipodia. We have demonstrated the presence of tropomyosins in lamellae of migrating cells using different antibodies against non-muscle tropomyosin in indirect immunofluorescence. Also, the distribution of tagged non-muscle tropomyosin isoforms was analyzed in transfected cells. We conclude that tropomyosin is present in lamellipodia, all the way to their advancing edges. The presence of tropomyosin in the leading edge urges for tropomyosin to be taken into account when modelling cell motility. Furthermore, the nature of cytosolic tropomyosin was investigated by gel filtration chromatography and the conclusion was that in fibroblasts, approximately 10% of the tropomyosin is present in the cytosol, while the remaining 90% is associated with actin microfilaments in the cytomatrix. Interestingly, the soluble tropomyosin was found to exist mostly in a multimeric form of high molecular weight. Surprisingly, skeletal muscle tropomyosin and recombinant TM1 expressed in Escherichia coli forms multimers, a phenomenon not observed previously.
Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2008. , 46 p.
cell motility, microfilament system, actin, tropomyosin
Biochemistry and Molecular Biology
Research subject Cell Biology
IdentifiersURN: urn:nbn:se:su:diva-7633ISBN: 978-91-7155-667-7OAI: oai:DiVA.org:su-7633DiVA: diva2:198734
2008-06-02, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 10:00
Stradal, Theresia, Dr
Lindberg, Uno, Professor Emeritus
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