Download or read book The Interaction of MAPs and Kinesin Motors with the Neuronal Cytoskeleton written by Jawdat Al-Bassam and published by . This book was released on 2003 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of neuronal architecture requires the microtubule and f-actin cytoskeleton. In developing neurons, the organization and dynamics of these cytoskeletal polymers are regulated by a diverse group of microtubule and f-actin associated proteins. However, microtubules and f-actin remain essential for the maintenance of neuronal architecture, as they are utilized as tracks by motor proteins for the transport a diverse organelles and macromolecules to and from the axons and dendrites. In this work, we investigate the conformations and biochemical activities of these two general classes of proteins. In chapter I, we show that although MAP2 and tau are unstructured in solution, they bind and fold onto the outer ridges of microtubule protofilaments. The extended MAP2 and tau conformations suggest that they stabilize microtubules by bridging multiple tubulins along protofilaments. Even though MAP2 and tau share homologous microtubule binding domains, we show in chapter II that this region of MAP2, but not the homologous region of tau, bind and bundles f-actin. We show that the MAP2-actin binding interaction is necessary for neurite initiation in cells. Based on this work, we propose that MAP2 may coordinate f-actin with microtubules during the neurite initiation process. In Chapter III, we studied the conformations of Unc104 kinesin; we show that the [alpha]-helices of the Unc104 neck can make two types of interactions: an intramolecular coiled coil in a monomeric motor, or an intermolecular coiled coil in a dimeric motor. Our work suggests the self-folding of the Unc104 neck regulates its dimerization, which is necessary for activation of fast processive motility. In chapter IV, we compared the microtubule binding interactions of Unc104 and conventional kinesin in the weak ADP state. We show that Unc104 and conventional kinesin bind microtubules with different binding modes; the Unc104.ADP binding is primarily mediated by the class conserved K-loop, whereas kinesin.ADP binding is mediated by the motor domain. However, MAP2 acts primarily as a competitive inhibitor of both motors binding to microtubules, in spite of their unique binding modes. A comparison of microtubule bound motor and MAP structures explains these biochemical observations, and suggests that steric hindrance due to the overlap of MAP and motor binding sites is primarily responsible for these inhibition effects. Our work suggests that the binding of MAPs and kinesins to microtubules must be locally regulated to prevent MAPS from interfering with organelle transport mediated by motor proteins. Our work suggests that MAPs and Kinesins utilize different strategies to bind the neuronal cytoskeleton. Furthermore, our work provides a number of examples supporting the notion that the evolution of different MAPs and kinesins has specified their polymer binding modes to their specialized functions in the cell.