| title: | Anti-titin monoclonal antibody Y1C7.A3 as a possible cellular and developmental marker in the cells of neural origin |
|---|---|
| reg no: | ETF6581 |
| project type: | Estonian Science Foundation research grant |
| subject: |
3.1. Basic Medicine |
| status: | accepted |
| institution: | TU Faculty of Medicine |
| head of project: | Aavo-Valdur Mikelsaar |
| duration: | 01.01.2006 - 31.12.2009 |
| description: | Annotatsioon: As one of results of previous studies (target foundation TARMP0421, ESF grants 5250 ja 5499, As LabAs finances), a monoclonal antibody was developed (named by us as Y1C7.A3) which antigen was repeatedly identified using MALDI-TOF and ESI-MS and proteomics database Swiss-Prot ja TrEMBL as titin (titin isoform ). In human foetal tissues, immunohistochemical analysis (performed so far) revealed specific expression of Y1C7.A3 antigen in brain, heart and striated muscles, blood vessels, lung alveoli, and glomeruli of kidney. In adult human heart and striated muscle cells, the antigen was expressed only in single cells, and irregularly. Surprisingly Y1C7.A3 antigen showed clear (though heterogeneous) expression in glial cells but not at least in one type of beta-III-tubulin positive neurons differentiated in vitro from neural stem cells. Very often it was possible to see distinct antigen deposits in cell bodies and neurites in cells differentiated in vitro for a long time. Antigen was not revealed in growth conus area. In addition, Y1C7.A3 antigen was expressed in vitro also in some large cells but not in granule cells themselves of rat granule cell cultures, and in vivo in certain areas of rat brain. There is very little data about the expression of titin in neural tissue. (Max A., et al. 1996 ; Schmidt M.M., et al. 2001; Zhao Y. et al., 2001). There is no information which titin isoforms could exist in this tissue not to speak about possible functions. However, our preliminary results allow to suppose that titin do express in cells of neural origin and might have an important role in the differentiation of certain types of neural cells. In this project, we plan research in the three main directions: 1. the investigation of location of Y1C7.A3 antigenic determinant in the titin molecule; also to elucidate whether the binding of anti-titin monoclonal antibodies onto neurofilament proteins found immunocytochemically is a real cross-reaction or there exists a four-componential titin-neurofilamental protein complex or both; 2. the investigation of the expression characteristics of Y1C7.A3 antigen (titin) at the level of mRNA and protein in neural stem cells and differentiating neural cells; to elucidate is it possible to use Y1C7.A3 as marker in the study of neural cell differentiation; the expression of Y1C7.A3 antigen will be studied also in other types of stem cells (limbal stem cells), and in tumour cells of neural origin (glioblastomas) 3. the investigation of the expression characteristics of Y1C7.A3 antigen (titin) at different developmental stages of rat brain on the ground of our findings that Y1C7.A3 antigen is expressed in vitro in rat granule cell culture only in certain type of large cells but not in granule cells themselves, and in vivo in different regions of rat brain; to elucidate is it possible to use Y1C7.A3 as a specific cellular and developmental marker in the development of brain tissue. We hope to get new information about the factors ( titin isoforms) taking part in the differentiation of the cells of neural origin. It is do possible that this new information enlarges our knowledge on the etiology and pathogenesis of some neurological diseases such as Sclerosis multiplex where overexpression of titin has been shown (Zhao Y. Et al.,2001) |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Anti Kalda | |||
| 2. | Ingrid Kalev | |||
| 3. | Aavo-Valdur Mikelsaar | Tartu Ülikool | ||
| 4. | Tõnu Püssa | |||
| 5. | Alar Sünter | |||
| 6. | Peeter Toomik | |||