Signal transduction and nuclear function of the human protocadherin hFat1

• Applicant: Professor Dr. Hans Werner Hofer (†)
• Subject Area: Cell Biology
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24184330

The giant human protein hFatl belongs to a superfamily of transmembrane proteins functioning in cell-cell recognition and adhesion. Although specific details of hFatl function have remained elusive, it is essential in podocyte formation of renal glomeruli and appears to have a central role in brain development and possibly the development of cell polarity. Recently, regulatory functions in actin dynamics and in the formation of cell-cell contacts have been reported . We provided evidence for a proteolytic release of the intracellular domain of hFatl and its translocation to the nucleus due to the unmasking of a nuclear localization sequence. Phosphorylation of the intracellular domain at tyrosine and serine residues may exert regulatory influences. Our experiments are intended (1) to clarify details of the proteolytic release of the intracellular domain of hFatl, (2) to provide information about Junctions of the isolated intracellular domain by studying its interactions with specific proteins recently identified by us (in particular scaffolding and transport proteins with reported nuclear functions: homer-3, a kinesin, and a heterologous nuclear RNA binding protein).

• DFG Programme: Research Grants