Prof. Dr. Stefan Veltel, Professor of Biotechnology, Hochschule Bremen, Bremen, Germany
Title of the talk:
Small GTPases in protein trafficking and diseases
Small G proteins (GTPases) are molecular switches cycling between a GTP-bound active state and a GDP-bound inactive state. GTP-hydrolysis leading to the inactive state is catalysed by GAP proteins (GTPase activating proteins), whereas GEF proteins (Guanine-nucleotide exchange factors) catalyse the nucleotide exchange leading to GTP-bound active GTPases in the cell. The GAP/GEF/GTPase circuits are part of a multitude of signal transduction pathways regulating cellular functions in health and disease. Two examples will be presented.
A. The retinitis pigmentosa 2 (RP2) gene is responsible for a particular variant of X chromosome–linked eye disease. Its gene product, the RP2 protein, is known to bind the GTP form of the small GTPase Arl3. Our crystallographic and biochemical data indicate a potential molecular mechanism explaining the prevalent patient mutations of X-linked Retinitis pigmentosa.
B. Numerous diseases such as cancer progression, inflammation and degenerative disorders are results of deregulated cell adhesion and migration. The integrin family of transmembrane cell surface receptors have a decisive impact on the migratory and invasive capacities of cancer and immune cells. It is becoming increasingly evident that not only activation/deactivation, but also the endo-/exocytic cycle of integrins plays an important role in mediating integrin function. The small Ras-family GTPase Rab21, which binds to the cytoplasmic tail of α-integrins, is a major mediator in the endocytic trafficking of integrins. We are currently identifying binding partner of Rab21 to understand the molecular mechanism of Rab21-dependent integrin trafficking.