Funcitonal analysis of keration-dependent melanosome and vesicle traffic in keratinocytes

• Applicant: Professor Dr. Thomas Magin
• Subject Area: Dermatology
• Term: from 2007 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40813012

The interaction between the cytoskeleton and organelles is essential for fundamental processes in cell polarity and vesicle transport. Melanosomes are lysosome-related organelles which protect the skin against UV light by forming supranuclear caps in keratinocytes. Melanosome biogenesis and transport in melanocytes depend on the regulation of actin and myosin motors by the GTPase Rab27a and Rab effectors and serve as an excellent model for this interaction. Little is known about transport and distribution of melanosomes in keratinocytes where they exert their major function. We have shown for the first time that loss of the keratin 5 (K5) gene causes Dowling-Degos Disease, characterized by hyperpigmentation, mistargeting of melanosomes and desmosomal cadherins. To analyze the mechanisms, we have isolated several keratin-binding proteins involved in vesicle transport. This leads to the hypothesis that K5 and K14 regulate the distribution of melanosomes and desmosomal cadherins in keratinocytes. Using melanosomes and desmosomal proteins as a paradigm to study a more general keratin function in vesicle transport, our project aims to understand the mechanisms at the molecular level. It will provide novel insights into the interdependence of intermediate filament proteins and organelle transport. In the long run, it may open new avenues to alter skin pigmentation.

• DFG Programme: Research Grants