Cell polarity: formin on the move

Formins assemble actin filaments that are typically arranged in long bundles. A new study has discovered that a fission yeast polarity formin transiently assembles short actin filaments at the cell tip, and then releases from the cortex and rides into the cell interior on filaments within the bundle.     

The GGA proteins: adaptors on the move

The GGA proteins are a family of ubiquitously expressed, Arf-dependent clathrin adaptors that mediate the sorting of mannose-6-phosphate receptors between the trans-Golgi network and endosomes. Recent studies have elucidated the biochemical and structural bases for the interaction of the GGA proteins with many binding partners, and have shed light on the molecular and cellular mechanisms by which the GGA proteins participate in protein sorting.     

Membrane proteins on the move.

The Keystone Symposium on Membrane protein structure/function relationships was held on 5-11 March 2001 in Tahoe City, California, USA.     

Where proteins and lipids meet: membrane trafficking on the move

The compartmental organization of eukaryotic cells has fascinated cell biologists for several decades. Detailed morphological, genetic, and biochemical studies have unraveled astonishingly complex molecular machineries involved in establishing and maintaining organelle identity and cell polarization. Many of the transport steps in the secretory and endocytic pathways are subject to manifold regulatory mechanisms, which in turn are interconnected with a plethora of signaling pathways. It therefore does not seem surprising that the cell biology of intracellular protein and lipid transport continues to thrive. The topics covered at the recent meeting on "Protein Transport in the Secretory Pathway" reflect the enormous complexity of how compartmentalization in eukaryotic cells is achieved.     

Elaborating polarity: PAR proteins and the cytoskeleton

Cell polarity is essential for cells to divide asymmetrically, form spatially restricted subcellular structures and participate in three-dimensional multicellular organization. PAR proteins are conserved polarity regulators that function by generating cortical landmarks that establish dynamic asymmetries in the distribution of effector proteins. Here, we review recent findings on the role of PAR proteins in cell polarity in C. elegans and Drosophila, and emphasize the links that exist between PAR networks and cytoskeletal proteins that both regulate PAR protein localization and act as downstream effectors to elaborate polarity within the cell.     

Ciliogenesis: building the cell's antenna

The cilium is a complex organelle, the assembly of which requires the coordination of motor-driven intraflagellar transport (IFT), membrane trafficking and selective import of cilium-specific proteins through a barrier at the ciliary transition zone. Recent findings provide insights into how cilia assemble and disassemble in synchrony with the cell cycle and how the balance of ciliary assembly and disassembly determines the steady-state ciliary length, with the inherent length-dependence of IFT rendering the ciliary assembly rate a decreasing function of length. As cilia are important in sensing and processing developmental signals and directing the flow of fluids such as mucus, defects in ciliogenesis and length control are likely to underlie a range of cilium-related human diseases.     

In and out of the postsynaptic region: signalling proteins on the move

Reversible translocation of signalling proteins to and from their sites of action has emerged as an important theme in signal transduction. The recent findings of the stimulus-induced translocation of Ca2+-calmodulin-dependent protein kinase II (CaMKII) and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor to and from the postsynaptic region are model cases for understanding how the dynamic localization of signalling proteins is used to regulate signal transduction.     

Cell polarity: Scaffold proteins par excellence

Par proteins are involved in determining cellular asymmetry. Recent studies have identified one of these proteins, Par6, as a key regulator of cell polarity and transformation via its interactions with small GTPases and atypical forms of protein kinase C.     

PDZ proteins and polarity: functions from the fly

Proteins that contain PDZ domains have been implicated in the localization of interacting partners to specific regions of the cell membrane. Although PDZ proteins that bind to a number of important mammalian proteins have been isolated, the significance of these interactions is unclear. In recent years, the fruit fly has emerged as a rich system for genetic analysis of PDZ protein function. Here, I discuss what the Drosophila data tell us about the roles and mechanisms of PDZ protein activity, and how this informs our understanding of PDZ function in other organisms.     

上皮极性蛋白的研究进展

极性蛋白（polarity protein）是指具有识别功能并且能够调节细胞极性的一类蛋白质,它们在许多生理和病理过程如细胞增殖、细胞凋亡、细胞迁移、损伤修复、上皮－间充质转化（epithelial—mesenchymal transition,EMT）中具有重要作用,也在肿瘤的发生和发展过程中起到重要作用。本文拟从上述几个方面对上皮相关极性蛋白的生物学功能做以综述,以期为疾病诊断和治疗提供新的思路。     

Giant proteins that move DNA: bullies of the genomic playground

As genetic material DNA is wonderful, but as a macromolecule it is unruly, voluminous and fragile. Without the action of DNA replicases, topoisomerases, helicases, translocases and recombinases, the genome would collapse into a topologically entangled random coil that would be useless to the cell. We discuss the organization, movement and energetics of these proteins that are crucial to the preservation of a molecule that has such beautiful biological but challenging physical properties.     

Par proteins and neuronal polarity

A hallmark of neurons is their ability to polarize with dendrite and axon specification to allow the proper flow of information through the nervous system. Over the past decade, extensive research has been performed in an attempt to understand the molecular and cellular machinery mediating this neuronal polarization process. It has become evident that many of the critical regulators involved in establishing neuronal polarity are evolutionarily conserved proteins that had previously been implicated in controlling the polarization of other cell types. At the forefront of this research are the partition defective (Par) proteins. In this review,we will provide a commentary on the progress of work regarding the central importance of Parproteins in the establishment of neuronal polarity.     

IAPs on the move: role of inhibitors of apoptosis proteins in cell migration

Inhibitors of Apoptosis Proteins (IAPs) are a class of highly conserved proteins predominantly known for the regulation of caspases and immune signaling. However, recent evidence suggests a crucial role for these molecules in the regulation of tumor cell shape and migration by controlling MAPK, NF-κB and Rho GTPases. IAPs directly control Rho GTPases, thus regulating cell shape and migration. For instance, XIAP and cIAP1 function as the direct E3 ubiquitin ligases of Rac1 and target it for proteasomal degradation. IAPs are differentially expressed in tumor cells and have been targeted by several cancer therapeutic drugs that are currently in clinical trials. Here, we summarize the current knowledge on the role of IAPs in the regulation of cell migration and discuss the possible implications of these observations in regulating tumor cell metastases.     

Mitotic internalization of planar cell polarity proteins preserves tissue polarity

Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also show PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically distributed PCP components risk mislocalization or unequal inheritance, which could have profound consequences for the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface, where asymmetry is re-established by a process reliant on neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize exhibit perturbed hair-follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this mechanism for regulating polarity during cell division.     

Establishing cell polarity by the Lgl family proteins

The lethal giant larvae (lgl) gene was first identified more than 30 years ago in Drosophila and characterized as a tumor suppressor gene. Studies in budding yeast, flies and mammals all indicate that the evolutionarily conserved Lgl family proteins play an important role in cell polarity. Sro7/77, the yeast Lgl homologues, are important for the establishment and reinforcement of cell polarity through their localized interaction and kinetic activation of the post-Golgi secretion machinery. As for higher eukaryotes, both in epithelial polarity and asymmetric cell division, the role of Lgl protein is deployed by localizing proteins to the membrane in a polarized fashion. In addition, Lgl is transiently required during the establishment phase of polarity, implicating that Lgl functions at strategic time points for proliferation control. Studies in cancer biology provide direct connections between malfunction of Lgl and formation, progression and metastasis of various cancers. Here, we review recent advances in the field, focusing on the function of the Lgl family in cellular polarization.     

Influence of extracellular matrix proteins on the expression of neuronal polarity

The influence of laminin (LN) and fibronectin (FN) on the differentiation of individual neurones from the embryonic rat central nervous system was studied in vitro. In control cultures or in the presence of soluble FN, most neurones had several dendrite-like and one axon-like processes. On substratum-bound LN, multipolar and unipolar cells were present. Soluble LN and bound FN induced a very simple neuronal morphology, most neurones having only one axon-like neurite as defined by morphological and immunocytochemical characteristics. The significant reduction of neuronal adhesion and spreading in conditions leading to the growth inhibition of dendrite-like processes suggests that, contrary to that of axons, dendrite growth strongly depends on neuronal adhesion. We propose a model in which the different dependency of axonal and dendritic outgrowth towards adhesion and spreading is explained by the respective physical properties of the two types of neurites.