UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that U...

UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophi...

Calcium and calmodulin-dependent protein kinase II (CaMKII) plays a fundamental role in the synaptic plasticity events that underlie learning and memory. Regulation of CaMKII kinase activity occurs through an autoinhibitory mechanism in which a regulatory domain of the kinase occupies the catalytic site and calcium/calmodulin activates the kinase by binding to and displacing this regulatory dom...

Ryanodine receptor channels regulate contraction of striated muscle by gating the release of calcium ions from the sarcoplasmic reticulum. Ryanodine receptors are expressed in excitable and non-excitable cells of numerous species, including the nematode C. elegans. Unlike vertebrates, which have at least three ryanodine receptor genes, C. elegans has a single gene encoded by the unc-68 locus. W...

Tissue-specific alternative pre-mRNA splicing is essential for increasing diversity of functionally different gene products. In Caenorhabditis elegans, UNC-60A and UNC-60B, nonmuscle and muscle isoforms of actin depolymerizing factor (ADF)/cofilin, are expressed by alternative splicing of unc-60 and regulate distinct actin-dependent developmental processes. We report that SUP-12, a member of a ...

In order to further understand the assembly and maintenance of the muscle contractile apparatus, we have identified a new protein, UNC-98, in the muscle of C. elegans. unc-98 mutants display reduced motility and a characteristic defect in muscle structure. We show that the major defect in the mutant muscle is in the M-lines and dense bodies (Z-line analogs). Both functionally and compositionall...

Septins are conserved GTPases that form heteromultimeric complexes and assemble into filaments that play a critical role in cell division and polarity. Results from budding and fission yeast indicate that septin complexes form around a tetrameric core. However, the molecular structure of the core and its influence on the polarity of septin complexes and filaments is poorly defined. The septin c...

The Caenorhabditis elegans UNC-45 protein is required for proper body wall muscle assembly and acts as a molecular co-chaperone for type II myosins. In contrast to other body wall muscle components, UNC-45 is also abundant in the germline and embryo. We show that maternally provided UNC-45 acts with non-muscle myosin II (NMY-2) during embryonic polarity establishment, cytokinesis and germline c...

Rac GTPases control cell shape by regulating downstream effectors that influence the actin cytoskeleton. UNC-115, a putative actin-binding protein similar to human abLIM/limatin, has previously been implicated in axon pathfinding. We have discovered the role of UNC-115 as a downstream cytoskeletal effector of Rac signaling in axon pathfinding. We show that unc-115 double mutants with ced-10 Rac...

The activity of transcription factors modulates several neural pathways that mediate complex behaviors. We describe here the role of the POU transcription factor UNC-86 in the olfactory behavior of Caenorhabditis elegans. unc-86-null mutants are defective in response to odor attractants but avoid odor repellents normally. Continuous UNC-86 activity is necessary for maintenance of odortaxis beha...