To identify sites of action of volatile anesthetics, we are studying genes in a functional pathway that controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans. The unc-1 gene occupies a central position in this pathway. Different alleles of unc-1 have unique effects on sensitivity to the different volatile anesthetics. UNC-1 shows extensive homology to human stomati...

unc-73 is required for cell migrations and axon guidance in C. elegans and encodes overlapping isoforms of 283 and 189 kDa that are closely related to the vertebrate Trio and Kalirin proteins, respectively. UNC-73A contains, in order, eight spectrin-like repeats, a Dbl/Pleckstrin homology (DH/PH) element, an SH3-like domain, a second DH/PH element, an immunoglobulin domain, and a fibronectin ty...

Mechanically gated ion channels are important modulators of coordinated movement, yet little is known of their molecular properties. We report that C. elegans unc-8, originally identified by gain-of-function mutations that induce neuronal swelling and severe uncoordination, encodes a DEG/ENaC family member homologous to subunits of a candidate mechanically gated ion channel. unc-8 is expressed ...

Anteroposterior cell migration and patterning in C. elegans are governed by multiple, interacting signaling pathways and transcription factors. In this study, we have investigated the role of ceh-20, the C. elegans ortholog of the HOX co-factor Extradenticle (Exd/Pbx), and unc-62, the C. elegans ortholog of Homothorax (Hth/Meis/Prep), in two processes that are regulated by Hox gene lin-39: cell...

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived f...

Wnt and Netrin signaling regulate diverse essential functions. Using a genetic approach combined with temporal gene expression analysis, we found a regulatory link between the Wnt receptor MOM-5/Frizzled and the UNC-6/Netrin receptor UNC-5. These two receptors play key roles in guiding cell and axon migrations, including the migration of the C. elegans Distal Tip Cells (DTCs). DTCs migrate post...

INTRODUCTION Intravenous immunoglobulin (IVIG) therapy is an effective treatment in patients with different diseases. This product must comply with all the regulatory requirements established by the World Health Organization and the European Pharmacopoeia for clinical tolerance, therapeutic efficacy, and viral safety. Although IVIG are effective and safe products, in some patients they may caus...

Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptoti...

Focal adhesions are multiprotein assemblages that link cells to the extracellular matrix. The transmembrane protein, integrin, is a key component of these structures. In vertebrate muscle, focal adhesion-like structures called costameres attach myofibrils at the periphery of muscle cells to the cell membrane. In Caenorhabditis elegans muscle, all the myofibrils are attached to the cell membrane...

Mutations in the unc-39 gene of C. elegans lead to migration and differentiation defects in a subset of mesodermal and ectodermal cells, including muscles and neurons. Defects include mesodermal specification and differentiation as well a neuronal migration and axon pathfinding defects. Molecular analysis revealed that unc-39 corresponds to the previously named gene ceh-35 and that the UNC-39 p...