Spatial Organization of Axonal Microtubules

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Dr. Heidemann proposes to gather preliminary information about two areas related to microtubule organization and neuronal growth. He proposes investigations of a working hypothesis for control of microtubule assembly by the advancing growth cone. In this model, tension of the neurite is the result of tension within the actin-based cytoskeleton of the neuron. This tension is supported by internal microtubules and by the culture substratum, placing both under compression. Structurally, this arrangement is similar to the architectural principle of tensegrity developed some years ago by Buckminster Fuller. Of particular importance, thermodynamic considerations lead to the result that compression on MTs may regulate MT elongation and thus provide an economical method for integrating MT assembly with growth cone movement. Three of the specific goals are an investigation of the role of microtubules in the unusually clear regionalization of cultured neurons into cell body, neurite and growth cone compartments. These compartments differ in their cytoskeleton and in their cell surface/cell cortex activity. Results in this and other laboratories suggest microtubules may regulate the activity of the cell cortex.