Catálogo de publicaciones - libros

Organelles, defined as intracellular membrane-bound structures in eukaryotic cells, were described from the early days of light microscopy and the development of cell theory in the 19^th century. During the 20^th century, electron microscopy and subcellular fractionation enabled the discovery of additional organelles and, together with radiolabel-ling, allowed the first modern experiments on their biogenesis. Over the past 30 years, the development of cell-free systems and the use of yeast genetics have together established the major pathways of delivery of newly synthesised proteins to organelles and the vesicular traffic system used to transfer cargo between organelles in the secretory and endocytic pathways. Mechanisms of protein sorting, retrieval and retention have been described and give each organelle its characteristic composition. Insights have been gained into the mechanisms by which complex organelle morphology can be established. Organelle biogenesis includes the process of organelle inheritance by which organelles are divided between daughter cells during mitosis. Two inheritance strategies have been described, stochastic and ordered, which are not mutually exclusive. Among the major challenges of the future are the need to understand the role of self-organization in ensuring structural stability and the mechanisms by which a cell senses the status of its organelles and regulates their biogenesis.

Protein sorting through the secretory and endocytic pathways is essential for many aspects of cell function, including the biogenesis and maintenance of numerous intra-cellular organelles. Efficient protein trafficking requires a complex machinery of regulatory and structural factors. Key components of this machinery include protein coats, which mediate selective recruitment of cargo and transport-vesicle formation and targeting. Through these functions, a diversity of protein coats, often with the aid of accessory factors, regulates protein type and number within secretory and endocytic organelles and at the cell surface. Recent studies both in model organisms and humans have provided new insights into the traditional view of protein coat structure and function. In addition, genetic and genome-based analyses have revealed novel coat components as well as the distinct sorting events in which they participate. The significance of these findings to secretory and endocytic sorting, and their relevance to the biogenesis of organelles comprising these pathways, are the subjects of the present review.

Membrane compartments in the secretory pathway retain their identity in spite of continuous membrane and protein flux through each compartment. A challenge in cell biology is to discover how compartment identity is established and maintained. A related issue is how protein and membrane cargo is sorted from resident molecules in a donor compartment and vectorially delivered to an acceptor compartment without compromise to the integrity of individual compartments. We review accumulating evidence indicating that compartmental identity is conferred combinatorially by members of key protein families (Rabs, ARFs, SNAREs) and lipid constituents (phosphoinositides). These molecules and their effectors participate in assembling exit sites in donor compartments that sort and package cargo, and entry sites in recipient compartments that mediate cargo entry without intermixing compartment constituents.

The endoplasmic reticulum (ER) adopts a number of structural forms that correlate with distinct functions. The differentiation, maintenance, and proliferation of these forms are only beginning to be understood. Differentiation and proliferation can be induced in the normal course of cell differentiation and by cellular stresses. Recent studies suggest that ER forms arise by a combination of self-organization and highly interconnected signaling and synthetic pathways. This review describes a number of ER ultrastructure forms, associated functions, and some of the potential mechanisms of their biogenesis.

The Golgi apparatus is a membrane-bounded organelle comprised of polarized stacks of cisternae and is required for trafficking of proteins and lipids within all eukaryotic cells. The Golgi, which is positioned centrally in the transport route between the endoplasmic reticulum (ER) and plasma membrane, is an organelle whose size, composition and morphology are effected by protein and lipid flux, as well as the cytoskeletal dynamics. The following chapter discusses various aspects of Golgi structure and function and recent insights into the dynamics of Golgi assembly.

Lysosomes are membrane-bound organelles that serve as the site for delivery of molecules destined for degradation. These molecules, along with lysosomal hydrolases, are delivered to lysosomes by a series of heterotypic vesicle fusion events. Lysosomes are also capable of homotypic fusion and yet cells are able to maintain a relatively constant size and number of lysosomes. To maintain lysosome size and number, highly regulated sorting and vesicle fission events must occur. The specificity of these processes is determined largely by targeting molecules that traffic vesicles to and away from lysosomes. Misregulated trafficking can result in alterations in the “normal” number and size of lysosomes within a cell. Such critical changes in lysosomes are often associated with human disease. The identification and characterization of the molecules involved in lysosome biogenesis and maintenance continues to advance our understanding of intracellular trafficking and endocytosis, as well as other basic cell biological processes.

The vertebrate cell nucleus undergoes disassembly and reassembly at each cell division. Elaborate and well-regulated mechanisms ensure faithful and precise cellular duplication throughout this process. This chapter is intended to summarize our current understanding of nuclear biogenesis, or nucleogenesis, with a specific focus on nuclear envelope assembly and nucleolar reformation following mitosis.

The mitochondrion is especially complex and interesting because of its prokaryotic origins and subsequent integration into the eukaryotic cell and establishment as an essential organelle. As a result of this evolutionary history, the mitochondrion is a mix of “old and new” biology. For example, this organelle has maintained its own small genome that codes for a handful of inner membrane proteins and utilizes a prokaryotic-like system for transcription and translation. In addition, novel pathways for mitochondrial biogenesis and movement within the cell have evolved concurrendy with its endosymbiosis. The importance of this unique organelle to cellular physiology is obvious from the broad spectrum of human diseases arising from defects in mitochondrial energy production, ion homeostasis, and morphology. The molecular mechanisms of mitochondrial biogenesis and protein import and export, as well as metal ion transport, are being dissected at a rapid pace and are the subjects of the following review.

Recent results have demonstrated that the molecular mechanisms of peroxisomal membrane biogenesis and the post-translational import of proteins into the organelle do not follow those paradigms established for other subcellular organelles. As such, we have much to learn about the peroxisome, and the human diseases that occur as a result of its malfunction. In this review, we describe how peroxisomes arise through these seemingly non-conventional processes, specifically focusing on how the organelle membrane assembles its constituent proteins, and how appropriate enzymes are imported. Particular emphasis is placed on identifying the role of specific peroxins at each step in the biosynthetic mechanism.