A Survey of Putative Secreted and Transmembrane Proteins Encoded in the C. elegans Genome

Background: Almost half of the Caenorhabditis elegans genome encodes proteins with either a signal peptide or atransmembrane domain. Therefore a substantial fraction of the proteins are localized to membranes, reside in thesecretory pathway or are secreted. While these proteins are of interest to a variety of different researchers rangingfrom developmental biologists to immunologists, most of secreted proteins have not been functionallycharacterized so far.Results: We grouped proteins containing a signal peptide or a transmembrane domain using various criteriaincluding evolutionary origin, common domain organization and functional categories. We found that putativesecreted proteins are enriched for small proteins and nematode-specific proteins. Many secreted proteins arepredominantly expressed in specific life stages or in one of the two sexes suggesting stage- or sex-specificfunctions. More than a third of the putative secreted proteins are upregulated upon exposure to pathogens,indicating that a substantial fraction may have a role in immune response. Slightly more than half of thetransmembrane proteins can be grouped into broad functional categories based on sequence similarity to proteinswith known function. By far the largest groups are channels and transporters, various classes of enzymes andputative receptors with signaling function.Conclusion: Our analysis provides an overview of all putative secreted and transmembrane proteins in C. elegans.This can serve as a basis for selecting groups of proteins for large-scale functional analysis using reverse geneticapproaches

GExplore: a web server for integrated queries of protein domains, gene expression and mutant phenotypes

<p>Abstract</p> <p>Background</p> <p>The majority of the genes even in well-studied multi-cellular model organisms have not been functionally characterized yet. Mining the numerous genome wide data sets related to protein function to retrieve potential candidate genes for a particular biological process remains a challenge.</p> <p>Description</p> <p>GExplore has been developed to provide a user-friendly database interface for data mining at the gene expression/protein function level to help in hypothesis development and experiment design. It supports combinatorial searches for proteins with certain domains, tissue- or developmental stage-specific expression patterns, and mutant phenotypes. GExplore operates on a stand-alone database and has fast response times, which is essential for exploratory searches. The interface is not only user-friendly, but also modular so that it accommodates additional data sets in the future.</p> <p>Conclusion</p> <p>GExplore is an online database for quick mining of data related to gene and protein function, providing a multi-gene display of data sets related to the domain composition of proteins as well as expression and phenotype data. GExplore is publicly available at: <url>http://genome.sfu.ca/gexplore/</url></p

IgCAMs redundantly control axon navigation in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) form one of the largest and most diverse families of adhesion molecules and receptors in the nervous system. Many members of this family mediate contact and communication among neurons during development. The <it>Caenorhabditis elegans </it>genome contains a comparatively small number of IgCAMs, most of which are evolutionarily conserved and found across all animal phyla. Only some of these have been functionally characterized so far.</p> <p>Results</p> <p>We systematically analyzed previously uncharacterized IgCAMs in <it>C. elegans</it>. Green fluorescent protein reporter constructs of 12 IgCAMs revealed that expression generally is not confined to a single tissue and that all tissues express at least one of the IgCAMs. Most IgCAMs were expressed in neurons. Within the nervous system significant overlap in expression was found in central components of the motor circuit, in particular the command interneurons, ventral cord motoneurons as well as motoneurons innervating head muscles. Sensory neurons are underrepresented among the cells expressing these IgCAMs. We isolated mutations for eight of the genes showing neuronal expression. Phenotypic analysis of single mutants revealed limited neuronal defects, in particular axon navigation defects in some of the mutants. Systematic genetic interaction studies uncovered two cases of functional overlap among three and four genes, respectively. A strain combining mutations in all eight genes is viable and shows no additional defects in the neurons that were analyzed, suggesting that genetic interactions among those genes are limited.</p> <p>Conclusion</p> <p>Genetic interactions involving multiple IgCAMs affecting axon outgrowth demonstrate functional overlap among IgCAMs during nervous system development.</p

Cell Autonomous Expression of Perlecan and Plasticity of Cell Shape in Embryonic Muscle ofCaenorhabditis elegans

AbstractPerlecan, a component of the extracellular matrix (ECM), is essential for myofilament formation and muscle attachment inCaenorhabditis elegans.We show here that perlecan is a product of muscle and that it behaves in a cell autonomous fashion. That is, perlecan expressed in an individual muscle cell does not spread beyond the borders of the ECM underlying that cell. Using a polyclonal antibody that recognizes all isoforms of perlecan, we demonstrate that this protein first appears extracellularly at the comma stage (approx. 350 min) of development. We also show that during morphogenesis muscle cells have a heretofore undescribed plasticity of shape. This ability to regulate cell shape allows cells within a muscle quadrant to compensate for missing cells and to form a functional quadrant. A dramatic example of this morphological flexibility can be observed in animals in which the D blastomere has been removed by laser ablation. Such animals, lacking 20 of the 81 embryonic body wall muscle cells, can survive to become viable adult animals indistinguishable from wildtype animals. This demonstrates that the assembly of an embryo via a stereotypic lineage does not preclude a more general regulation during morphogenesis. It appears that embryos are flexible enough to immediately compensate for drastic alterations in tissue composition, a feature of development that may be of general importance during evolution

Cell Autonomous Expression of Perlecan and Plasticity of Cell Shape in Embryonic Muscle ofCaenorhabditis elegans

AbstractPerlecan, a component of the extracellular matrix (ECM), is essential for myofilament formation and muscle attachment inCaenorhabditis elegans.We show here that perlecan is a product of muscle and that it behaves in a cell autonomous fashion. That is, perlecan expressed in an individual muscle cell does not spread beyond the borders of the ECM underlying that cell. Using a polyclonal antibody that recognizes all isoforms of perlecan, we demonstrate that this protein first appears extracellularly at the comma stage (approx. 350 min) of development. We also show that during morphogenesis muscle cells have a heretofore undescribed plasticity of shape. This ability to regulate cell shape allows cells within a muscle quadrant to compensate for missing cells and to form a functional quadrant. A dramatic example of this morphological flexibility can be observed in animals in which the D blastomere has been removed by laser ablation. Such animals, lacking 20 of the 81 embryonic body wall muscle cells, can survive to become viable adult animals indistinguishable from wildtype animals. This demonstrates that the assembly of an embryo via a stereotypic lineage does not preclude a more general regulation during morphogenesis. It appears that embryos are flexible enough to immediately compensate for drastic alterations in tissue composition, a feature of development that may be of general importance during evolution

The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2–mediated axon guidance

The L1 cell adhesion molecule (L1CAM) participates in neuronal development. Mutations in the human L1 gene can cause the neurological disorder CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus). This study presents genetic data that shows that L1-like adhesion gene 2 (LAD-2), a Caenorhabditis elegans L1CAM, functions in axon pathfinding. In the SDQL neuron, LAD-2 mediates dorsal axon guidance via the secreted MAB-20/Sema2 and PLX-2 plexin receptor, the functions of which have largely been characterized in epidermal morphogenesis. We use targeted misexpression experiments to provide in vivo evidence that MAB-20/Sema2 acts as a repellent to SDQL. Coimmunoprecipitation assays reveal that MAB-20 weakly interacts with PLX-2; this interaction is increased in the presence of LAD-2, which can interact independently with MAB-20 and PLX-2. These results suggest that LAD-2 functions as a MAB-20 coreceptor to secure MAB-20 coupling to PLX-2. In vertebrates, L1 binds neuropilin1, the obligate receptor to the secreted Sema3A. However, invertebrates lack neuropilins. LAD-2 may thus function in the semaphorin complex by combining the roles of neuropilins and L1CAMs