Functional Analysis of Protein Interactions at Microtubule Tips

Due to a temporary embargo, Chapter 6 and Appendix B cannot yet be made available at RePub.Microtubules are a part of the cytoskeleton involved in many essential processes, such as intracellular transport of cargoes, cell migration, positioning of cellular organelles and formation of the mitotic spindle for chromosome segregation. The fast growing end of microtubules (the plus-end) can interact with specific microtubule plus-end binding proteins (also known as plus-end tracking proteins, or +TIPs). +TIPs participate in microtubule interactions with different cellular structures and control microtubule dynamics. This thesis describes the functional analysis of protein interactions at the microtubule plus-ends. The microtubule plus-end tracking protein CLIP-170 (cytoplasmic linker protein of 170 kDa) regulates its association with microtubules by changing its conformation. The folded head-to-tail conformation of CLIP-170 inhibits microtubule association and also interferes with the binding of dynactin and LIS1 to the CLIP-170 COOH terminus. The functional relationship of CLIP family members with three EB family members EB1, EB2 and EB3 is described. CLIPs bind directly to the COOH terminus of the E

Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein)

Several microtubule binding proteins, including CLIP-170 (cytoplasmic linker protein-170), CLIP-115, and EB1 (end-binding protein 1), have been shown to associate specifically with the ends of growing microtubules in non-neuronal cells, thereby regulating microtubule dynamics and the binding of microtubules to protein complexes, organelles, and membranes. When fused to GFP (green fluorescent protein), these proteins, which collectively are called +TIPs (plus end tracking proteins), also serve as powerful markers for visualizing microtubule growth events. Here we demonstrate that e

Hb BOSKOOP [HBA2c.112C > T p.Pro38Ser]: A NEW alpha 2 CHAIN VARIANT OBSERVED IN A MORROCAN FAMILY

Genetics of disease, diagnosis and treatmen