Cain NE et al. (2015) Nucleus "SUN proteins and nuclear envelope spacing."

Cain NE, Starr DA

[Nucleus, 2015]

The nuclear envelope consists of 2 membranes separated by 30-50 nm, but how the 2 membranes are evenly spaced has been an open question in the field. Nuclear envelope bridges composed of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins have been proposed to set and regulate nuclear envelope spacing. We tested this hypothesis directly by examining nuclear envelope spacing in Caenorhabditis elegans animals lacking UNC-84, the sole somatic SUN protein. SUN/KASH bridges are not required to maintain even nuclear envelope spacing in most tissues. However, UNC-84 is required for even spacing in body wall muscle nuclei. Shortening UNC-84 by 300 amino acids did not narrow the nuclear envelope space. While SUN proteins may play a role in maintaining nuclear envelope spacing in cells experiencing forces, our data suggest they are dispensable in most cells.

Zhou K et al. (2010) Dev Dyn "Movers and shakers or anchored: Caenorhabditis elegans nuclei achieve it with KASH/SUN."

Zhou K, Hanna-Rose W

[Dev Dyn, 2010]

The invariant cell division patterns that characterize Caenorhabditis elegans development make it an ideal system to study the mechanisms that control nuclear movement and positioning. Forward genetic screens in this system allowed identification of the key molecular machinery for connecting the nucleus to the cytoskeleton; pairs of protein partners, consisting of a KASH domain protein and a SUN domain protein, bridge the nuclear envelope to connect the nucleus to cytoskeletal components. The C. elegans genome encodes several KASH/SUN pairs, and mutant phenotypes as well as tissue-specific expression patterns suggest a diversity of functions. These functions include moving the nucleus but have been extended to effects on the chromosomes inside the nucleus as well. We review the impact of the C. elegans system in pioneering this field as well as the functions of these KASH/SUN protein pairs across spatial and temporal C. elegans development.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Best AM et al. (2018) Cell Microbiol "Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophilla."

Best AM, Kwaik YA

[Cell Microbiol, 2018]

Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.

Horn HF (2014) Curr Top Dev Biol "LINC complex proteins in development and disease."

Horn HF

[Curr Top Dev Biol, 2014]

The LINC complex spans the nuclear envelope and plays critical roles in coordinating nuclear and cytoplasmic activities and in organizing nuclear and cytoskeletal features. LINC complexes are assembled from KASH and SUN-domain proteins, which interact in the nuclear envelope and form a physical link between the cytoskeleton and the nuclear interior. A number of diseases have been associated with mutations in genes coding for LINC complex proteins. Mouse models of LINC complex protein have provided valuable insight into LINC complex functions and into how these proteins contribute to the various diseases with which they have been associated.

Starr DA et al. (2003) J Cell Sci "ANChors away: an actin based mechanism of nuclear positioning."

Han M, Starr DA

[J Cell Sci, 2003]

Mechanisms for nuclear migration and nuclear anchorage function together to control nuclear positioning. Both tubulin and actin networks play important roles in nuclear positioning. The actin cytoskeleton. has been shown to position nuclei in a variety of systems from yeast to plants and animals. It can either act as a stable skeleton to anchor nuclei or supply the active force to move nuclei. Two C elegans genes and their homologues play important roles in these processes. Syne/ANC-1 anchors nuclei by directly tethering the nuclear envelope to the actin cytoskeleton, and UNC-84/SUN functions at the nuclear envelope to recruit Syne/ANC-1.

Lee SK et al. (2013) Int J Biochem Cell Biol "Dicarbonyl/l-xylulose reductase (DCXR): The multifunctional pentosuria enzyme."

Ahnn J, Lee SK, Son LT, Choi HJ

[Int J Biochem Cell Biol, 2013]

Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive -dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.

Wilhelmsen K et al. (2006) J Cell Sci "KASH-domain proteins in nuclear migration, anchorage and other processes."

Wilhelmsen K, Truong H, Ketema M, Sonnenberg A

[J Cell Sci, 2006]

The nucleus in eukaryotic cells can move within the cytoplasm, and its position is crucial for many cellular events, including migration and differentiation. Nuclear anchorage and movement can be achieved through association of outer nuclear membrane (ONM) proteins with the three cytoskeletal systems. Two decades ago studies described C. elegans mutants with defects in such events, but only recently has it been shown that the strategies for nuclear positioning are indeed conserved in C. elegans, Drosophila, mammals and potentially all eukaryotes. The integral ONM proteins implicated in these processes thus far all contain a conserved Klarsicht/ANC-1/Syne homology (KASH) domain at their C-terminus that can associate with Sad1p/UNC-84 (SUN)-domain proteins of the inner nuclear membrane within the periplasmic space of the nuclear envelope (NE). The complex thus formed is responsible not only for association with cytoplasmic elements but also for the integrity of the NE itself.

Woglar A et al. (2014) Chromosoma "Chromosome movement in meiosis I prophase of Caenorhabditis elegans."

Woglar A, Jantsch V

[Chromosoma, 2014]

Rapid chromosome movement during prophase of the first meiotic division has been observed in many organisms. It is generally concomitant with formation of the "meiotic chromosome bouquet," a special chromosome configuration in which one or both chromosome ends attach to the nuclear envelope and become concentrated within a limited area. The precise function of the chromosomal bouquet is still not fully understood. Chromosome mobility is implicated in homologous chromosome pairing, synaptonemal complex formation, recombination, and resolution of chromosome entanglements. The basic mechanistic module through which forces are exerted on chromosomes is widely conserved; however, phenotypic differences have been reported among various model organisms once movement is abrogated. Movements are transmitted to the chromosome ends by the nuclear membrane-bridging SUN/KASH complex and are dependent on cytoskeletal filaments and motor proteins located in the cytoplasm. Here we review the recent findings on chromosome mobility during meiosis in an animal model system: the Caenorhabditis elegans nematode.

Bone CR et al. (2016) J Cell Sci "Nuclear migration events throughout development."

Bone CR, Starr DA

[J Cell Sci, 2016]

Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a variety of important developmental models. Genetic approaches to identify mutations that disrupt nuclear migration in yeast, filamentous fungi, Caenorhabditis elegans, Drosophila melanogaster and plants led to the identification of microtubule motors, as well as Sad1p, UNC-84 (SUN) domain and Klarsicht, ANC-1, Syne homology (KASH) domain proteins (LINC complex) that function to connect nuclei to the cytoskeleton. We focus on how these proteins and various mechanisms move nuclei during vertebrate development, including processes related to wound healing of fibroblasts, fertilization, developing myotubes and the developing central nervous system. We also describe how nuclear migration is involved in cells that migrate through constricted spaces. On the basis of these findings, it is becoming increasingly clear that defects in nuclear positioning are associated with human diseases, syndromes and disorders.