THESIS
2013
xii, 116 pages : illustrations (some color) ; 30 cm
Abstract
Centrosome is one major type of microtubule organizing center in animal cells localizing on
the microtubule minus ends. Centrosome regulates the nucleation of microtubules, anchoring
of the polymerized microtubules and it duplicates only once in one cell cycle. End binding
protein 1 (EB1), on the other hand, is an important protein localized on the microtubule plus
ends, recruiting other plus tip interacting proteins to function in cytoskeleton regulation. Recent
studies show that EB1 is also a steady component of centrosomes while the actual function of
centrosomal EB1 is yet to be clearly defined. In this study, I aim at generating a comprehensive
map of EB1 protein interactions and investigating the mechanisms by which its binding proteins
are involved in centrosome organizat...[
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Centrosome is one major type of microtubule organizing center in animal cells localizing on
the microtubule minus ends. Centrosome regulates the nucleation of microtubules, anchoring
of the polymerized microtubules and it duplicates only once in one cell cycle. End binding
protein 1 (EB1), on the other hand, is an important protein localized on the microtubule plus
ends, recruiting other plus tip interacting proteins to function in cytoskeleton regulation. Recent
studies show that EB1 is also a steady component of centrosomes while the actual function of
centrosomal EB1 is yet to be clearly defined. In this study, I aim at generating a comprehensive
map of EB1 protein interactions and investigating the mechanisms by which its binding proteins
are involved in centrosome organization. I performed a genome wide prediction for new EB1
binding proteins and verified at least four new EB1 interacting proteins. One EB1 binding
protein GAS2L1, positioning on the centriole proximal ends, was required for centrosome
separation in G2, which is the prerequisite for bipolar spindle formation. My research suggests
that GAS2L1 involved centrosome separation depends on an intact cytoskeleton network, both
actins and microtubules, and EB1 association. The activity of GAS2L1 is regulated in a cell
cycle dependent manner. After mitosis, centrosomes would recruit new PCM proteins onto
them. Another EB1 binding protein, CDK5RAP2, has been found to act as a scaffold for
anchoring other PCM components like γ-tubulin ring complex. In my study, the mechanism of
how CDK5RAP2 can act highly dynamically on centrosomes is revealed and I show a dynein-dynactin
based transportation is critical for CDK5RAP2 centrosomal recruitment. My research
on these EB1 related centrosome proteins elucidates the importance of their functions on
regulating the centrosome organization and also suggests potential role of EB1 on the
centrosome.
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