Review Articles in 2008

Thetrans-Golgi network (TGN) is a major sorting centre for lipids and proteins that lies at the crossroads of endocytic and exocytic pathways. Recent studies have started to elucidate the molecular machineries that function in sorting and trafficking at the TGN.

Cells that undergo apoptosis are demolished in a controlled manner that minimizes damage to neighbouring cells and avoids the release of immunostimulatory molecules. These events are orchestrated primarily by a family of cysteine proteases called caspases, which target hundreds of proteins for restricted proteolysis.

Our understanding of the biological functions of small non-coding RNAs has been fostered by the analysis of genetic deletions of individual microRNAs (miRNAs) in mammals. These studies show that miRNAs are key regulators of animal development and are potential human disease loci.

The Rpd3/Hda1 family of protein lysine deacetylases has numerous substrates and diverse functions. Whereas class I enzymes are multiprotein histone deacetylase complexes that are crucial for chromatin modification and transcriptional regulation, some class II enzymes function as signal transducers that are regulated by nucleocytoplasmic translocation.

Ribosomes have been the focus of structural and biochemical studies for more than 50 years. Recently, high-resolution structures have provided molecular snapshots of different intermediates in ribosome-mediated translation in atomic detail, which has revolutionized our understanding of the mechanism of protein synthesis.

Type 2 diabetes is projected to afflict 300 million people worldwide by 2020. Therefore, a deeper understanding of the processes and mechanisms that lead to metabolic failure in key tissues and organ systems in patients with type 2 diabetes is urgently required.

Recent studies have provided insights into the mechanisms that regulate DNA repair in specific cell-cycle phases and the pathways that ensure cell-cycle progression or arrest in normal and cancerous cells. Understanding how DNA repair is modulated during the cell cycle has important applications.

Oxygen is required for the survival of most organisms. Recent advances show that it is not only important for the promotion of cellular bioenergetics and metabolism, but also that it is an essential signal that regulates cell fate during embryonic development and in stem cells.

A detailed model of the composition and structure of membranes exists. But how do cells orchestrate numerous enzymes, as well as the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?

Numerous protein domains bind to membrane phospholipids and drive the relocalization of proteins that are involved in crucial cell-signalling and membrane-trafficking events. Precise control of the timing and location of membrane association involves several mechanisms.

Inositols and their derivatives are versatile molecules that have varied functions and distributions across the three kingdoms of life. How is it that inositol derivatives became ubiquitous and diverse in eukaryotes, and how might the various functions of these molecules have emerged during eukaryote diversification?

Cholesterol is an essential structural component in the cell membranes of most vertebrates. Increased understanding of the metabolism and functional compartmentalization of cholesterol and how this is related to the organ systems level should provide insights into the physiology of cholesterol trafficking.

The sphingolipids constitute an important class of bioactive lipids that includes ceramide and sphingosine-1-phosphate (S1P). Deciphering the cellular functions of sphingolipids requires an understanding of the complex metabolic pathways and the mechanisms that regulate lipid generation and lipid action.

Lipids function as extracellular and intracellular messengers in a complex lipid signalling network that controls important cellular processes. Imbalances in this network contribute to the pathogenesis of different diseases, including cancer, inflammation and metabolic syndrome, which therefore share common points of therapeutic intervention.

The family of Argonaute proteins has important roles in RNA-mediated gene silencing. Argonaute proteins form complexes with small non-coding RNAs such as small interfering RNAs and microRNAs, control protein synthesis and mRNA stability, and participate in the production of a new class of small RNAs, Piwi-interacting RNAs.

The balance between stem cell self-renewal and differentiation is ultimately controlled by the integration of intrinsic factors with extrinsic cues supplied by the surrounding microenvironment, known as the stem cell niche. How much do we know about this intriguing microenvironment?

Mammalian iron homeostasis is achieved through iron acquisition and storage. Intestinal iron absorption and macrophage-mediated recycling of iron from red blood cells are highly regulated. The discovery of iron transporters and insight into their regulation has provided important information about iron-related disorders.

Extracellular signals can be transduced across the plasma membrane by activating G-protein-coupled receptors. The conformational changes induced in the receptor on ligand binding and how this causes the activation of the associated G protein are beginning to be understood.

Kinetochores are large proteinaceous structures that link centromeric DNA to spindle microtubules. More than 80 kinetochore proteins have been identified so far, and recent analyses are revealing how these proteins function to direct kinetochore specification and assembly, bind to microtubules and regulate chromosome segregation.

BCL-2 family proteins have either pro- or anti-apoptotic activities that are crucial for the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. Recent advances suggest that interactions between BCL-2 family proteins affect their localization and conformation and regulate their bioactivity.