To branch or not to branch: regulation of microtubules and neuronal morphology by PSD-95 and cypin

Neuronal morphology is crucial for normal communication and health and is altered in many disease states. Microtubules are key regulators of neuronal morphology and are key components in transport of molecular cargo. Therefore, regulation of microtubule behavior is very important for establishing proper neuronal morphology and function. Thus, we examined the role of two proteins, PSD-95 and cypin, on microtubule dynamics and structure. First we show that PSD-95, a well-known synaptic protein, negatively regulates dendrite branching through a novel interaction with EB3, a plus-end microtubule-binding protein. Second, we show that cypin, a protein known to positively regulate dendrite branching, alters microtubule behavior and binds to assembled microtubules as well as tubulin heterodimers. We also show that PSD-95 and cypin have opposite but complimentary roles in changing microtubule stability, with cypin increasing and PSD-95 decreasing the stability of microtubules. Finally, we examine the ability of small molecules compounds to modify the cellular functions of cypin. We show that cypin’s guanine deaminase activity and interaction with PSD-95 can be altered by these compounds, affecting cellular behavior.Ph. D.Includes bibliographical referencesIncludes vitaby Eric S. Swee