Sorting and Recycling Endosomes provides the latest information on endosomes, the receiving compartment for endocytosed cargos, and the donor compartment and sorting station for cargos designated to lysosomes, Golgi, or plasma membrane. In recent years, the importance of endosomes as a sorting and recycling compartment has become increasingly appreciated. As such, scientists from various fields of cell biology, membrane traffic, and beyond, see the needs to communicate and learn about the methods used to investigate the dynamics and functions of endosomes. This book brings together specialists from the field who contribute their expertise on a broad range of biomedical topics that will provide ideal reading for researchers interested in endosomal sorting and recycling. This volume covers the approaches necessary to study the key components that mediate the generation and transport of membrane-bounded carriers from the endosomes, and how membrane trafficking machinery is coordinated with cytoskeletons during these processes. In addition to studies carried out in mammalian cells, other model systems such as worm and yeast are also included. - Provides the latest information on endosomes, the receiving compartment for endocytosed cargos, and the donor compartment and sorting station for cargos designated to lysosomes, Golgi, or plasma membrane. - Covers an increasingly appreciated field in cell biology - Includes both established and new technologies - Brings together specialists from the field who contribute their expertise on a broad range of biomedical topics that will provide ideal reading for researchers interested in endosomal sorting and recycling

Endocytic recycling is the process by which cells return internalized cargos and receptors back to plasma membrane. Efficient recycling of cargos requires ordered transport of cargos from early endosome to recycling endosome. This is mainly achieved through the coordination of small GTPase RAB-5 and RAB-10. The small GTPase RAB-5 is a master regulator of cargo sorting at the early endosome and RAB-10 is a key resident of the recycling endosome. Countercurrent cascades of GEFs and GAPs for Rab proteins have been proposed to mediate Rab conversion, a process in which early acting Rabs are inactivated by later acting Rabs. Here we demonstrate that a downstream Rab protein, RAB-10, binds to and recruits a RAB-5 GAP, TBC-2, onto endosomes to inactivate the upstream Rab, RAB-5. This process is critical for proper relay of cargos from RAB-5 controlled early endosomes to RAB-10 regulated recycling endosomes. Lack of TBC-2 disrupted RAB-5/RAB-10 interaction and caused accumulation of recycling cargo hTAC-GFP in a malfunctioned hybrid early-recycling endosome compartment. Furthermore, our study showed that this cargo transition process from early to recycling endosome also requires the concerted effort by a BAR-domain protein AMPH-1, which acts as a binding partner and a contributor to the recruitment of TBC-2 on endosomes. In addition, the C. elegans Rac1 homolog CED-10 can also bind and recruit it to endosomes. Taken together, our worked showed that RAB-10, AMPH-1 and CED-10 act in a concerted manner and recruits TBC-2 to inactivate RAB-5. These interactions are essential for early-to-recycling endosome transition and endocytic recycling. We further demonstrated here that RAB-10, recruits CNT-1, the C. elegans homolog of mammalian ACAP1 and ACAP2 (Arf6 GTPase-activating proteins) to inactivate ARF-6 and downregulate endosomal PI(4,5)P2, a key phosphoinositide in membrane traffic.

Endosomes are a heterogeneous population of endocytic vesicles and tubules that have captivated the interest of biologists for many years, partly due to their important cellular functions and partly due to their intriguing nature and dynamics. Endosomes represent a fascinating interconnected network of thousands of vesicles that transport various cargoes, mainly proteins and lipids, to distant cellular destinations. How endosomes function, what co-ordinates the molecular determinants at each step of their dynamic life cycle and what their biological and medical relevance is, are among the questions addressed in this book.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a highly prevalent hereditary renal disorder in which fluid-filled cysts are appeared in both kidneys. Main causative genes of ADPKD are PKD1 and PKD2, encoding for polycystin-1 (PC1) and polycystin-2 (PC2) respectively. Those proteins are localized on primary cilia and function as mechanosensor in response to the fluid flow, translating mechanistic stimuli into calcium signaling. With mutations either of PKD1 or PKD2, hyper-activated renal tubular epithelial cell proliferation is observed, followed by disrupted calcium homeostasis and aberrant intracellular cyclic AMP (cAMP) accumulation. Increased cell proliferation with fluid secretion leads to the development of thousands of epithelial-lined, fluid-filled cysts in kidneys. It is also accompanied by interstitial inflammation, fibrosis, and finally reaching end-stage renal disease (ESRD). In human ADPKD, the age at which renal failure typically occurs is later in life, however no specific targeted medications are available to cure ADPKD. Recently, potential therapeutic targets or surrogate diagnostic biomarkers for ADPKD are proposed with the advances in the understanding of ADPKD pathogenesis, and some of them were attempted for clinical trials. Herein, we will summarize genetic and epi-genetic molecular mechanisms in ADPKD progression, and overview the currently available biomarkers or potential therapeutic reagents suggested.

This book summarizes all new data obtained after development of methods of Golgi complex sub fractionation, molecular biology and microscopy. It collects the full range of expertise, different points of view and different approaches. The book is devoted to molecular modes of the function of the Golgi apparatus as a whole, taking into account all experimental data. The book aims to make the functional organization of the Golgi apparatus more understandable.

Epidermal Langerhans Cells focuses on epidermal Langerhans cells (LCs) and the important role they play in the induction of contact hypersensitivity and graft rejection. This in-depth work discusses how these antigen-presenting cells are modulated by various physicochemical agents (such as UV light) and how they can be infected by the AIDS virus. It also reveals that cytokines mediate their development into potent T cell-stimulatory dendritic cells. This comprehensive review covers important experimental details and methods, and fascinating information on LCs. It also provides an overview of the immune system as it relates to the skin in health and disease. This up-to-date publication is an indispensable resource for all investigative and clinical dermatologists, as well as immunologists interested in antigen-presenting cells.

During my thesis work I studied membrane sorting in the endocytic pathway, in mammalian cells and in the amoeba "Dictyostelium discoideum". In the first part (1), I studied sorting of membrane proteins devoid of known endocytosis signals. My results show that, in addition to cytoplasmic tails of membrane proteins, then transmembrane regions determine whether they are excluded or not from clathrincoated pits, and thus controls their access to endosomal compartmemts. In the second part (2), I studied membrane sorting during phagocytosis and macropinocytosis. I used for this the amoeba "Dictyostelium discoideum". My results show that several plasma membrane proteins are excluded from the membrane of the newly formed phagosome. This exclusion starts in the membrane delimiting the phagocytic and the macropinocytic cups. Analysis of mutant strains revealed that clathrin-associated adaptor complexes were not necessary for this selective exclusion. In third part (3), I characterized the previously uncharacterized recycling endosomes in "Dictyostelium discoideum"