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The secretory and endocytic pathways in eukaryotic cells serve as major routes for protein transport out of and into the cell. Proteins enter the secretory pathway by translocation into the endoplasmic reticulum. Subsequent protein transport between organelles of the secretory pathway is mediated in large part by membranous carriers that bud from a donor organelle membrane then dock and fuse with...
Secretory proteins enter the ER after or concomitant with their synthesis on cytoplasmic ribosomes in a process known as translocation. In either case, nascent secretory proteins must be targeted to the translocation machinery at the ER membrane and must traverse the lipid bilayer of the ER through the translocation channel. Molecular chaperones in the cytosol and ER lumen assist translocation and...
Transport of lipid and protein within the early secretory pathway is mediated by small transport vesicles that act as molecular taxis, shuttling cargoes between the endoplasmic reticulum (ER) and Golgi apparatus and within the Golgi. These vesicles are sculpted from donor organelles by distinct sets of cytoplasmic coat proteins that deform the lipid bilayer into a highly curved structure while selecting...
Eukaryotic cells use multiple pathways for the endocytic entry of proteins and lipids at the plasma membrane. To date, the best characterized pathway is clathrin-mediated endocytosis. This chapter presents an overview of the mechanisms of clathrin-mediated endocytosis and how itis regulated. We provide a mechanistic description of how a clathrin-coated vesicle (CCV) is formed, from the stages of initiation...
Dense core granules (DCGs) are vesicular organelles derived from outbound traffic through the eukaryotic secretory pathway. As DCGs are formed, the secretory pathway can also give rise to other types of vesicles, such as those bound for endosomes, lysosomes, and the cell surface. DCGs differ from these other vesicular carriers in both content and function, storing highly concentrated cores’ of condensed...
Trafficking pathways of eukaryotic cells exhibit sophisticated interplay between protein and lipid components. The protein molecules and their interacting networks are fairly well characterised. However, the lipid components and their regulation are much less understood. In this chapter, we describe our current understanding of how lipid dynamics can contribute to intracellular trafficking, based...
Membrane traffic pathways require the transport of material between successive organelles, which in neurons may be more than one meter apart. This traffic involves a varied mix of microtubule- and actin-based motility, driven by dynein, kinesin family members and myosins. In this chapter, we will describe the morphology and movement of me membrane carriers that transport material between organelles...
The movement of proteins between compartments of the secretory and endocytic pathways occurs via vesicles and/or larger carriers. The efficacy of both pathways relies on high fidelity with which the vesicles are delivered to the appropriate target membrane. The initial recognition between a vesicle and a target membrane appears to be mediated by members of loosely related family of tethering factors...
Fusion of biological membranes plays an important role in cell structure and function. It is essential for organelle biogenesis, vesicle targeting, constitutive and regulated exocytosis, endocytosis, pathogen invasion of host cells, sperm-egg fusion and skeletal muscle formation. This chapter summarizes our current knowledge of the mechanisms of intracellular membrane fusion with particular emphasis...
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