WormBook : the online review of C. elegans biology最新文献

Neurotransmitters signal via G protein coupled receptors (GPCRs) to modulate activity of neurons and muscles. C. elegans has ∼150 G protein coupled neuropeptide receptor homologs and 28 additional GPCRs for small-molecule neurotransmitters. Genetic studies in C. elegans demonstrate that neurotransmitters diffuse far from their release sites to activate GPCRs on distant cells. Individual receptor types are expressed on limited numbers of cells and thus can provide very specific regulation of an individual neural circuit and behavior. G protein coupled neurotransmitter receptors signal principally via the three types of heterotrimeric G proteins defined by the G alpha subunits Gαo, Gαq, and Gαs. Each of these G alpha proteins is found in all neurons plus some muscles. Gαo and Gαq signaling inhibit and activate neurotransmitter release, respectively. Gαs signaling, like Gαq signaling, promotes neurotransmitter release. Many details of the signaling mechanisms downstream of Gαq and Gαs have been delineated and are consistent with those of their mammalian orthologs. The details of the signaling mechanism downstream of Gαo remain a mystery. Forward genetic screens in C. elegans have identified new molecular components of neural G protein signaling mechanisms, including Regulators of G protein Signaling (RGS proteins) that inhibit signaling, a new Gαq effector (the Trio RhoGEF domain), and the RIC-8 protein that is required for neuronal Gα signaling. A model is presented in which G proteins sum up the variety of neuromodulator signals that impinge on a neuron to calculate its appropriate output level.

Members of the protein superfamily of small guanosine triphosphatases, also known as small GTPases, small G-proteins, or the Ras superfamily, are involved in nearly every aspect of cell biology. Small GTPases are tightly regulated molecular switches that make binary on/off decisions through controlled loading of GTP (activation) and hydrolysis of GTP to GDP (inactivation). Small GTPases typically function as nodal points that integrate broad upstream regulatory inputs and disseminate broad effector outputs. The superfamily comprises five families that are conserved across eukaryotes: Ras, Rho, Rab, Arf, and Ran. Each family, besides Ran, has radiated functionally since our last common ancestor with fungi, and certain subfamilies persist throughout metazoa. The double genome duplication leading to vertebrates resulted in two to four genes for many subfamilies, plus some novel mammalian additions. Here we discuss general principles of small GTPase biology, survey the C. elegans complement of small GTPases and how they compare to their mammalian counterparts, and note atypical nematode members that do not fall into discrete subfamilies. We do not discuss the multitude of other proteins with catalytic guanosine triphosphatase domains that fall outside the small GTPase/Ras superfamily.

Dauer diapause is a stress-resistant, developmentally quiescent, and long-lived larval stage adopted by Caenorhabditis elegans when conditions are unfavorable for growth and reproduction. This chapter contains methods to induce dauer larva formation, to isolate dauer larvae, and to study pre- and post-dauer stages.

Genetic nomenclature for Caenorhabditis species and other nematodes is supervised by WormBase in collaboration with the Caenorhabditis Genetics Center (CGC) and with essential input from the community of scientists working on C. elegans and other nematodes.

The C. elegans tubulin family is composed of nine α-, six β-, and one γ-tubulin. Tubulins are highly conserved, functioning as α-β heterodimers that assemble into microtubules. These cylindrical and ubiquitous components of the cytoskeleton are critical for nearly all cellular and developmental processes. C. elegans has provided a model for the study of microtubules in multiple settings including separation of chromosomes, cellular polarity, and neuronal sensation. Tubulins and microtubules interact with a long list of other cellular proteins that regulate tubulin homeostasis, modify microtubule dynamics, and control incorporation into or disassociation of higher-order cellular structures such as spindles or ciliary axonemes. A collection of enzymes modifies tubulins, often at the variable carboxyl-terminal tail, adding another layer of regulation to microtubule structure and function. Genetic and cytological studies in C. elegans have revealed roles for tubulin and its associated proteins in numerous contexts from embryogenesis to adult behavior.

In all animals, oocytes are surrounded by an extracellular matrix upon fertilization. This matrix serves similar purposes in each animal. It functions to mediate sperm binding, to prevent polyspermy, to control the chemical environment of the embryo, and to provide physical protection to the embryo as it developes. The synthesis of the C. elegans matrix, or eggshell, begins when the oocyte enters the spermatheca and is fertilized by a single sperm. The process of eggshell synthesis is thought to take place during the completion of the maternal meiotic divisions such that the multi-layered eggshell is completed by anaphase II. The synthesis of the eggshell occurs in a hierarchical pattern in which the outermost layers are synthesized first in order to capture and retain the innermost layers as they form. Recent studies have revealed that the lipid-rich permeability barrier is distinct from the outer trilaminar eggshell. These new findings alter our previous understanding of the eggshell. This chapter aims to define each of the eggshell layers and the molecules that are known to play significant roles in their formation.

The nematode Caenorhabditis elegans is now a major model organism in biology. The choice of Sydney Brenner to adopt this species in the mid-1960s and the success of his team in raising it to a model organism status have been told (http://www.wormbook.org/toc_wormhistory.html; Brenner, 2001; Ankeny, 2001). Here we review the pre-Brenner history of the use of free-living nematodes as models for general questions in biology. We focus on the period that started in 1899 with the first publication of Emile Maupas mentioning Rhabditis elegans and ended in 1974 with the first publications by Brenner. A common thread in this period, aided by the variety in modes of reproduction of different nematode species, is found in studies of meiosis, fertilization, heredity, and sex determination. Maupas in his 1900 opus on reproduction had already chosen C. elegans as the species of reference. Hikokura Honda determined its hermaphrodite chromosomal content in 1925. C. elegans was again isolated and chosen as a main subject by Victor Nigon in the 1940-50s. Nigon mastered crosses between C. elegans hermaphrodites and males, described the meiotic behavior of chromosomes in XX hermaphrodites and X0 males and, using tetraploids, correctly inferred that sex was determined by X chromosome to autosome dosage. With Ellsworth Dougherty, Nigon isolated and studied a C. briggsae body size mutant and a C. elegans slow growth mutant. Dougherty and his team devoted most of their work to finding a defined culture medium to screen for physiological mutants, focusing on C. briggsae. With Helene Fatt, Dougherty also performed the first genetic study of natural variation in C. elegans, concerning the difference in heat resistance of the Bergerac and Bristol strains. Jean Brun, a student of Nigon, performed a long and remarkable experiment in acclimatization of C. elegans Bergerac to higher temperatures, the significance of which remains to be clarified.

In C. elegans, mutants that are defective in muscle function and/or structure are easy to detect and analyze since: 1) body wall muscle is essential for locomotion, and 2) muscle structure can be assessed by multiple methods including polarized light, electron microscopy (EM), Green Fluorescent Protein (GFP) tagged proteins, and immunofluorescence microscopy. The overall structure of the sarcomere, the fundamental unit of contraction, is conserved from C. elegans to man, and the molecules involved in sarcomere assembly, maintenance, and regulation of muscle contraction are also largely conserved. This review reports the latest findings on the following topics: the transcriptional network that regulates muscle differentiation, identification/function/dynamics of muscle attachment site proteins, regulation of the assembly and maintenance of the sarcomere by chaperones and proteases, the role of muscle-specific giant protein kinases in sarcomere assembly, and the regulation of contractile activity, and new insights into the functions of the dystrophin glycoprotein complex.

Strongyloides is a genus of parasitic nematodes that, unusually, has a free-living adult generation. Here we introduce the biology of this genus, especially the fascinating but complex life-cycle, together with an overview of the taxonomy, morphology, genetics, and genomics of this genus.