Proper neuronal development and function requires precise sorting and delivery of various elements from the soma to the synapse. Important mediators of intracellular transport events are the actin-based class V myosin motors, which are involved in organelle transport in various cell types. Two myosin V family members, myosin Va and Vb, are present in the brain, however, the identity of cargoes transported by these motors is unknown. The objective of this thesis was to conduct molecular and cell biological studies to identify and characterize novel myosin V cargoes in neurons. The first approach I used was to characterize the distribution of candidate protein cargoes after blocking the function of endogenous myosin Va and Vb with dominant-negative (DN) versions. I found that in developing neurons, expression of DN myosin Vb, but not DN myosin Va, resulted in the accumulation in the soma of the AMPA-type glutamate receptor subunit, GluR1, and a reduction of its surface expression. I also found that myosin Vb-mediated trafficking of GluR1 required an interaction with the GTPase Rab11. These results reveal a novel mechanism for the transport of a specific glutamate receptor subunit mediated by myosin Vb and Rab11. As an alternative approach to identify myosin Va binding partners in the brain, we conducted a yeast-two hybrid screen of a rat brain cDNA library using the cargo binding domain of myosin Va. Among the proteins identified in our screen, I selected a protein of unknown function previously identified as Rab-lysosomal-interacting protein like 2 (RILPL2) and further assessed its function. I found that RILPL2 expression in non-neuronal cells resulted in morphological changes and activation of the Rho GTPase Rac1. In developing neurons, gain or loss of RILPL2 function altered the density of dendritic spine protrusions and increased phosphorylation of the Rac1 effector Pak. These findings uncover a novel role for the myosin Va-interacting protein, RILPL2, in regulati.

This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.

Gain a quick and easy understanding of this complex subject with the 2nd edition of Cellular Physiology and Neurophysiology by doctors Mordecai P. Blaustein, Joseph PY Kao, and Donald R. Matteson. The expanded and thoroughly updated content in this Mosby Physiology Monograph Series title bridges the gap between basic biochemistry, molecular and cell biology, neuroscience, and organ and systems physiology, providing the rich, clinically oriented coverage you need to master the latest concepts in neuroscience. See how cells function in health and disease with extensive discussion of cell membranes, action potentials, membrane proteins/transporters, osmosis, and more. Intuitive and user-friendly, this title is a highly effective way to learn cellular physiology and neurophysiology. Focus on the clinical implications of the material with frequent examples from systems physiology, pharmacology, and pathophysiology. Gain a solid grasp of transport processes—which are integral to all physiological processes, yet are neglected in many other cell biology texts. Understand therapeutic interventions and get an updated grasp of the field with information on recently discovered molecular mechanisms. Conveniently explore mathematical derivations with special boxes throughout the text. Test your knowledge of the material with an appendix of multiple-choice review questions, complete with correct answers Understand the latest concepts in neurophysiology with a completely new section on Synaptic Physiology. Learn all of the newest cellular physiology knowledge with sweeping updates throughout. Reference key abbreviations, symbols, and numerical constants at a glance with new appendices.

This text is an introduction to the interface between the actin cytoskeleton and the myriad of issues fundamental to the understanding of the nervous system. It covers the neurobiology of actin ranging from basic cellular organization and function to the roles of actin in the health and disease states of the nervous system. Its opening chapter presents the fundamental concepts required to appreciate the details of the molecular machinery that regulates actin in a cellular context, setting the stage for the first part of the book which reviews the neurobiology of actin at the cellular level. The latter section of the book then discusses the functions of actin in the context of neurobiological issues ranging from early development to synaptic function and disease states of the nervous system. This text is intended for neuroscientists interested in investigating the actin cytoskeleton in the context of their particular neuroscience research program, and its chapters are cross-referenced in order to assist readers in finding relevant information that is covered in greater depth in other chapters.

This book discusses the primary functions of microtubule-associated proteins (MAPs) such as MAP2 and tau in neuronal morphogenesis, as well as relationships between neuronal differentiation and the expression of neuronal intermediate filaments (nestin, alpha internexin, and neurofilament triplet proteins). It emphasizes the importance of several cytoskeletal proteins for neuronal differentiation and morphogenesis, organelle transport, and synaptic functions. The book considers the involvement of tau MAPs in the formation of paired helical filaments in Alzheimer's disease, and it examines the mechanisms of organelle transports and molecular motors such as kinesin, braindynein, and kinesin superfamily proteins. Cytoskeletal proteins involved in synaptic formation and transmitter release and new synaptic junctional-associated proteins are explored as well.