Pirri JK et al. (2012) Curr Opin Neurobiol "The neuroethology of C. elegans escape."

Pirri JK, Alkema MJ

[Curr Opin Neurobiol, 2012]

Escape behaviors are crucial to survive predator encounters. Touch to the head of Caenorhabditis elegans induces an escape response where the animal rapidly backs away from the stimulus and suppresses foraging head movements. The coordination of head and body movements facilitates escape from predacious fungi that cohabitate with nematodes in organic debris. An appreciation of the natural habitat of laboratory organisms, like C. elegans, enables a comprehensive neuroethological analysis of behavior. In this review we discuss the neuronal mechanisms and the ecological significance of the C. elegans touch response.

Kimble JE (1994) Science "An ancient molecular mechanism for establishing embryonic polarity?"

Kimble JE

[Science, 1994]

Worms, butterflies, and chimpanzees all have the same body axes-head and tail, front and back, and left and right sides. How are these axes established during development? Is there a single molecular map used by most metazoan embryos or have similar coordinates been achieved during evolution by diverse routes? A comparison of the mechanisms that establish body axes in distantly related organisms can begin to answer this fundamental question.

Goodman MB et al. (2017) Pflugers Arch "The extraordinary AFD thermosensor of C. elegans."

Sengupta P, Goodman MB

[Pflugers Arch, 2017]

The nematode C. elegans exhibits complex thermal experience-dependent navigation behaviors in response to environmental temperature changes of as little as 0.01C over a >10C temperature range. The remarkable thermosensory abilities of this animal are mediated primarily via the single pair of AFD sensory neurons in its head. In this review, we describe the contributions of AFD to thermosensory behaviors and temperature-dependent regulation of organismal physiology. We also discuss the mechanisms that enable this neuron type to adapt to recent temperature experience and to exhibit extraordinary thermosensitivity over a wide dynamic range.

Garcia LR et al. (2016) Curr Opin Neurobiol "Neural circuits for sexually dimorphic and sexually divergent behaviors in Caenorhabditis elegans."

Portman DS, Garcia LR

[Curr Opin Neurobiol, 2016]

Increasing interest in sex differences in Caenorhabditis elegans neurobiology is resulting from several advances, including the completion of the male tail connectome and the surprising discovery of two 'new' neurons in the male head. In this species, sex-specific circuits in the hermaphrodite and male control reproductive behaviors such as egg-laying and copulation, respectively. Studies of these systems are revealing interesting similarities and contrasts, particularly in the mechanisms by which nutritional status influences reproductive behaviors. Other studies have highlighted the importance of sexual modulation of shared neurons and circuits in optimizing behavioral strategies. Together, these findings indicate that C. elegans uses intertwined, distributed sex differences in circuit structure and function to implement sex-specific as well as sexually divergent, shared behaviors.

Munoz MJ (2003) Mech Ageing Dev "Longevity and heat stress regulation in Caenorhabditis elegans."

Munoz MJ

[Mech Ageing Dev, 2003]

Aging is the most complex phenotype for a multicellular organism. This process is now being under severe investigation. Here I will review the different processes known to affect longevity in the nematode Caenorhabditis elegans and their relationship with thermotolerance. All the longevity mutants that have been tested so far show an increase in stress resistance. In particular, long-lived mutants affected in the IGF/insulin pathway and those affected in the germ-line formation are both thermotolerant and long-lived. The mechanisms that activate the stress resistance are now been understood including the DAF-16 fork head transcription factor transport to the nucleus and the activation of genes involved in the defense to stress. The high correlation between stress resistance and longevity suggests that the same molecular activities that defend the cell from stress can defend the cell from the damage caused by aging.

Zahn JM et al. (2007) Curr Opin Biotechnol "Systems biology of aging in four species."

Kim SK, Zahn JM

[Curr Opin Biotechnol, 2007]

Using DNA microarrays to generate transcriptional profiles of the aging process is a powerful tool for identifying biomarkers of aging. In Caenorhabditis elegans, a number of whole-genome profiling studies identified genes that change expression levels with age. High-throughput RNAi screens in worms determined a number of genes that modulate lifespan when silenced. Transcriptional profiling of the fly head identified a molecular pathway, the ''response to light'' gene set, that increases expression with age and could be directly related to the tendency for a reduction in light levels to extend fly''s lifespan. In mouse, comparing the gene expression profiles of several drugs to the gene expression profile of caloric restriction identified metformin as a drug whose action could potentially mimic caloric restriction in vivo. Finally, genes in the mitochondrial electron transport chain group decrease expression with age in the human, mouse, fly, and worm.

Kalhammer G et al. (2000) Essays Biochem "Unconventional myosins."

Bahler M, Kalhammer G

[Essays Biochem, 2000]

Myosins constitute a large superfamily of F-actin-based motor proteins found in many organisms from yeast to humans. A phylogenetic comparison of their head sequences has allowed them to be grouped into 15 different classes. Unconventional myosins can be monomeric or dimeric, but are thought not to form filaments, unlike conventional myosin. The double-headed class-V myosins are good candidates for transporting vesicles, organelles and (mRNA) particles along actin filaments. Class-I myosins are involved in membrane dynamics and actin organization at the cell cortex, thus affecting cell migration, endocytosis, pinocytosis and phagocytosis. A class-III myosin from Drosophila is required for phototransduction and maintenance of the rhabdomere. Class-IX myosins negatively regulate the small G-protein Rho, a signalling molecule that regulates the organization of the actin cytoskeleton. Protein kinases that are regulated by members of the Rho small G-protein family regulate the motor activities of different myosins.

McLachlan AD (1984) Annual Review of Biophysics & Bioengineering "Structural implications of the myosin amino acid sequence."

McLachlan AD

[Annual Review of Biophysics & Bioengineering, 1984]

Many questions about the action of muscle would be answered if we knew the atomic structures of both myosin and actin. The analysis of complete myosin genes and the sequencing of amino acids are vital steps towards this end. Genetic analysis identifies the different variants of myosin that exist in each animal, and the study of mutants will help to distinguish essential parts of the molecule. New cloned genes with changed functions will soon be constructed. The amino acid sequence places the important active groups and structural units of this very large protein in their correct framework. It also helps to show how the individual molecules form into regular arrays in the thick filaments of muscle. Under the electron miscroscope, individual myosin molecules appear to have long, thin rodlike tails with two globular heads emerging in a forked configuration at one end. Each molecule is a doublet containing two, paired myosin chains. The rod part is approximately 1500 A long and 20 A in diameter, while the heads are elongated, with a diameter of 70 A and length of up to 200 A. The main protein subunit of myosin is called the heavy chain. The unc-54 gene heavy chain from the soil nematode worm Caenorhabditis elegans contains 1966 amino acids (Figures 1 and 2). Figure 1 also shows part of M. Elzinga's chemical sequence from the head of rabbit skeletal muscle for comparison. The rod sequence from nematode alone contains 7-residue and 28-residue repeats, so it is laid out in zones of 28 amino acids with its own local numbering system (1' to 1117') indicated in the rest of this article by primes. Other sequences and special features marked in the Figures are described later. This review concentrates on structural aspects of muscle, excluding chemical kinetics and the dynamics of contraction. We begin with a short account of basic facts. Next we consider the myosin genes and the topography of the active regions in the head. An analysis of regularities in the rod sequence then leads on to questions about thick filaments packing and the mechanical flexibility of the

Verstraeten VL et al. (2007) Curr Med Chem "The nuclear envelope, a key structure in cellular integrity and gene expression."

Ramaekers FC, van Steensel MA, Broers JL, Verstraeten VL

[Curr Med Chem, 2007]

The envelope that encapsulates the cell nucleus has recently gained considerable interest, as several clinical syndromes are linked to mutations in its molecular components. Most disorders recognized so far are caused by defects in the nuclear lamins, building blocks of a filamentous network lining the nucleoplasmic side of the inner nuclear membrane. Nuclear lamins are the evolutionary precursors of cytoskeletal intermediate filaments and associate in a head-to-tail manner into a stable lamina at the nuclear periphery and into a more dispersed structure in the nucleoplasm. Lamins have a scaffolding function for several nuclear processes such as transcription, chromatin organization and DNA replication, and maintain nuclear and cellular integrity. Mutations in the LMNA gene, encoding A-type lamins, can cause cardiac and skeletal muscle disease, lipodystrophy and premature ageing phenotypes. Hence, the integrity of the nuclear envelope seems essential for longevity. Furthermore, the laminopathies provide evidence that metabolism and ageing are as tightly linked in humans as they are in model organisms such as C. elegans. In this review, we elaborate on the structure and functions of nuclear lamins, the spectrum of syndromes related to mutations in nuclear envelope components and pathogenic concepts unifying these disorders.

Alan JK et al. (2013) Small GTPases "Mutationally activated Rho GTPases in cancer."

Lundquist EA, Alan JK

[Small GTPases, 2013]

The Rho family of GTPases (members of the Ras superfamily) are best known for their roles in regulating cytoskeletal dynamics. It is also well established that misregulation of Rho proteins contributes to tumorigenesis and metastasis. Unlike Ras proteins, which are frequently mutated in cancer (around 30%), Rho proteins themselves are generally not found to be mutated in cancer. Rather, misregulation of Rho activity in cancer was thought to occur by overexpression of these proteins or by misregulation of molecules that control Rho activity, such as activation or overexpression of GEFs and inactivation or loss of GAPs or GDIs. Recent studies, enabled by next-generation tumor exome sequencing, report activating point mutations in Rho GTPases as driver mutations in melanoma, as well as breast, and head and neck cancers. The Rac1(P29L) mutation identified in these tumor studies was previously identified by our lab as an activating Rac mutation in C. elegans neuronal development, highlighting the conserved nature of this mutation. Furthermore, this finding supports the relevance of studying Rho GTPases in model organisms such as C. elegans to study the mechanisms that underlie carcinogenesis. This review will describe the recent findings that report activating Rho mutations in various cancer types, moving Rho GTPases from molecules misregulated in cancer to mutagenic targets that drive tumorigenesis.