In vivo functions of CD 44

• Applicant: Professor Dr. Peter Herrlich
• Subject Area: Cell Biology
• Term: from 2000 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5281312

The term CD44 designates a family of transmembrane proteins encoded by one unique gene. Due to alternative splicing of ten "variant" exons, the family exhibits great variability in protein structure. Members of the CD44 family play important roles in normal embryonic development such as limb formation, in the immune response and in hematopoiesis and are involved in pathological processes such as carcinogenic tansformation, tumor metastasis and autoimmune diseases. The extracellular conformation and therefore the extracellular properties of CD44 proteins are influenced from inside the cell by splice regulation, glycosylation, phosphorylation of the cytoplasmic tail and interactions of the cytoplasmic tail with intracellular proteins. The extracellular portion serves to interact with other cells or with the ECM thereby mediating outside-in signalling and influencing the activity of intracellular proteins, e.g. ezrin or merlin. Based on our previous work we request support for the following goals: i) Regulation of cell growth by ezrin and merlin both of which seem to interact with CD44. ii) Identification of factors and mechanisms that are involved in regulated alternative splicing. iii) Identification of mechanisms substituting for CD44 functions in CD44-/- mice.

• DFG Programme: Research Grants