The 18 kDa translocator protein (TSPO) is an integral membrane protein known to be involved in porphyrin transport and heme biosynthesis. TSPO also plays a role in modulating immune response, regulation of cell proliferation and programmed cell death. TSPO is associated with several health conditions such as ischemic heart reperfusion, cancers and neurodegenerative diseases. While the potential of TSPO as a major therapeutic target has been well recognized, the lack of detailed understanding of its function and ligand binding sites have hindered drug design. In this thesis we will describe the expression, extraction and purification of Rhodobacter sphaeroides TSPO (RsTSPO). Rhodobacter is one of the closest ancestors of mitochondria and RsTSPO can be used as a model for mammalian TSPO. RsTSPO was overexpressed in E. coli, and it was extracted from the membranes with detergent (i.e. n-dodecylphosphocoline (DPC) and n-dodecyl-ß-D-maltoside (DDM)) then purified by Ni-affinity and size exclusion chromatographies. The RsTSPO could be expressed and purified in high yield (mg quantitites), high purity, and in its functional state. Binding studies of RsTSPO were performed utilizing fluorescence quenching of intrinsic tryptophans with a number of porphyrins ligands such as protoporphyrin IX (PPIX), hemin, meso-Tetra(4-sulfonatophenyl)porphine dihydrochloride (2HTPPS), Zn (II) meso-Terta(4-sulfonatophenyl)porphine dihydrochloride (ZnTPPS) and with the diagnostic ligand, PK11195. Binding studies of RsTSPO were performed in both detergents (DPC and DDM) to assess the effect of the membrane mimic environment on binding. We will also describe the first evidence of the catalytic activity of the purified RsTSPO under ambient light in the presence of molecular oxygen on its natural ligand, protoporphyrin IX. We will demonstrate the photodegradation of protoporphyrin IX by RsTSPO in the presence of oxygen and light. In addition, we have studied the effect of molecular oxygen and reactive oxygen scavengers (sodium azide and glutathione) on the decomposition of protoporphyrin IX. Also, we will describe preliminary NMR studies in an effort to characterize the ligand binding site(s) of TSPO. We have performed both solution and solid state NMR studies on pure RsTSPO and RsTSPO-ligand complexes.

This book is a printed edition of the Special Issue "Translocator Protein (TSPO)" that was published in IJMS

Plant cells house highly dynamic cytoskeletal networks of microtubules and actin microfilaments. They constantly undergo remodeling to fulfill their roles in supporting cell division, enlargement, and differentiation. Following early studies on structural aspects of the networks, recent breakthroughs have connected them with more and more intracellular events essential for plant growth and development. Advanced technologies in cell biology (live-cell imaging in particular), molecular genetics, genomics, and proteomics have revolutionized this field of study. Stories summarized in this book may inspire enthusiastic scientists to pursue new directions toward understanding functions of the plant cytoskeleton. The Plant Cytoskeleton is divided into three sections: 1) Molecular Basis of the Plant Cytoskeleton; 2) Cytoskeletal Reorganization in Plant Cell Division; and 3) The Cytoskeleton in Plant Growth and Development. This book is aimed at serving as a resource for anyone who wishes to learn about the plant cytoskeleton beyond ordinary textbooks.

Systems Neuroscience in Depression provides a comprehensive overview of the normal and depressed brain processes as studied from a systems neuroscience perspective. Systems neuroscience uses a wide variety of approaches to study how networks of neurons form the bases of higher brain function. A broad overview is discussed starting with a background from neurodevelopment and neural understanding as well as novel treatment approaches for depression. This book covers basic developmental aspects and depressive psychopathology, as well as the basic scientific background from animal models and experimental research. Current advances in systems neuroscience are highlighted in studies from child and adolescent psychiatry. Integrated approaches are presented with regards to genetics, neuroimaging and neuroinflammation as well as neuroendocrinology. The field of systems and network neuroscience is evolving rapidly and this book provides a greatly needed resource for researchers and practitioners in systems neuroscience and psychiatry. Knowledge covering the whole life span from early to later life Comprehensively written chapters developing from molecules via epigenetics and neural circuits to clinical neuroscience Understanding the neurobiology of major depressive disorder Integrating stress and environmental factors with molecular underpinnings More than 25 illustrations and tables

This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes, autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.