Phosphoinositides And Disease

Phosphoinositides (PIs) are minor components of cellular membranes that play critical regulatory roles in several intracellular functions. This book describes the main enzymes regulating the turnover of each of the seven PIs in mammalian cells, some of their intracellular functions and some evidence of their involvement in human diseases. Due to the complex inter-relation between the distinct PIs and the plethora of functions that they can regulate inside a cell, this book is not meant to be a comprehensive coverage of all aspects of PIs signalling but rather an overview on the current state of the field and where it could go from here. Phosphoinositide and inositol phosphates interact with and modulate the recruitment and activation of key regulatory proteins and in doing so control diverse functions including cell growth and proliferation, apoptosis, cytoskeletal dynamics, insulin action, vesicle trafficking and nuclear function. Initially, inositide signaling was limited to the PLC pathway; however, it is now clear that all the seven phosphoinositides and more than 30 different inositol phosphates likely have specific signaling functions. Moreover there is a growing list of proteins that are regulated by inositol signaling. This has raised the question as to how inositol signaling can control diverse processes and yet maintain signaling specificity. Controlling the levels of inositol signaling molecules and their subcellular compartmentalisation is likely to be critical. This meeting will bring together scientists from different backgrounds to discuss how understanding inositol signaling may be used to target complex human diseases that manifest themselves when inositol signaling is deregulated.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.

PI3K has become a very intense area of research, with over 2000 publications on PI3K in PubMed for 2009 alone. The expectations for a therapeutic impact of intervention with PI3K activity are high, and progress in the clinical arena is being monitored by many. However, targeted therapies almost invariably encounter roadblocks, often exposing unresolved questions in the basic understanding of the target

There are scattered reports in the published literature citing relationships between actin, actin-binding proteins and disease. This volume brings this information together for the first time, with a focus on human disorders. The volume is relevant to a wide readership including cell biologists interested in understanding how structural and functional changes in proteins impact on the organism as a whole.

Cells of the immune system are activated by a variety of stimuli that are derived from other cells, ingested material or from invading microorganisms. This issue of CTMI focuses on the mechanisms of phosphoinositide-mediated protein recruitment to intracellular membranes.