Candidatus Dormibacterota is an uncultured bacterial phylum found predominantly in soil that is present in high abundances within cold desert soils. Here, we interrogate nine metagenome-assembled genomes (MAGs), including six new MAGs derived from soil metagenomes obtained from two eastern Antarctic sites. Phylogenomic and taxonomic analyses revealed these MAGs represent four genera and five species, representing two order-level clades within Ca.
View Article and Find Full Text PDFSphingosine 1-phosphate (S1P) is an essential lipid metabolite that signals through a family of five G protein-coupled receptors, S1PR1-S1PR5, to regulate cell physiology. The multiple sclerosis drug Fingolimod (FTY720) is a potent S1P receptor agonist that causes peripheral lymphopenia. Recent research has demonstrated direct neuroprotective properties of FTY720 in several neurodegenerative paradigms; however, neuroprotective properties of the native ligand S1P have not been established.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment and no cure. Mutations in were identified as a cause of familial ALS (fALS) in 2012. We investigated the functional impact of mutant profilin 1 expression in spinal cords during mouse development.
View Article and Find Full Text PDFOvercoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics.
View Article and Find Full Text PDFUnlabelled: Tropomyosins, a family of actin-associated proteins, bestow actin filaments with distinct biochemical and physical properties which are important for determining cell shape and regulating many cellular processes in eukaryotic cells. Here, we used RNA-seq to investigate the effect of four tropomyosin isoforms on gene expression in undifferentiated and differentiated rat B35 neuroblastoma cells. In undifferentiated cells, overexpression of tropomyosin isoforms Tpm1.
View Article and Find Full Text PDFGenetically encoded filamentous actin probes, Lifeact, Utrophin and F-tractin, are used as tools to label the actin cytoskeleton. Recent evidence in several different cell types indicates that these probes can cause changes in filamentous actin dynamics, altering cell morphology and function. Although these probes are commonly used to visualise actin dynamics in neurons, their effects on axonal and dendritic morphology has not been systematically characterised.
View Article and Find Full Text PDFRegulation of the actin cytoskeleton is dependent on a plethora of actin-associated proteins in all eukaryotic cells. The family of tropomyosins plays a key role in controlling the function of several of these actin-associated proteins and their access to actin filaments. In order to understand the regulation of the actin cytoskeleton in highly dynamic subcellular compartments of neurons such as growth cones of developing neurons and the synaptic compartment of mature neurons, it is pivotal to decipher the functional role of tropomyosins in the nervous system.
View Article and Find Full Text PDFInhibitory proteins, particularly Nogo 66, a highly conserved 66-amino-acid loop of Nogo A (an isoform of RTN4), play key roles in limiting the intrinsic capacity of the central nervous system (CNS) to regenerate after injury. Ligation of surface Nogo receptors (NgRs) and/or leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue the paired immunoglobulin-like receptor B (PIRB) by Nogo 66 transduces inhibitory signals that potently inhibit neurite outgrowth. Here, we show that soluble leukocyte immunoglobulin-like receptor A3 (LILRA3) is a high-affinity receptor for Nogo 66, suggesting that LILRA3 might be a competitive antagonist to these cell surface inhibitory receptors.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and familial ALS accounts for 10% of cases. The identification of familial ALS mutations in the actin-binding protein profilin 1 directly implicates actin dynamics and regulation in the pathogenesis of ALS. The mechanism by which these mutations cause ALS is unknown.
View Article and Find Full Text PDFBackground: The actin cytoskeleton is critically involved in the regulation of neurite outgrowth.
Results: The actin cytoskeleton-associated protein tropomyosin induces neurite outgrowth in B35 neuroblastoma cells and regulates neurite branching in an isoform-dependent manner.
Conclusions: Our data indicate that tropomyosins are key regulators of the actin cytoskeleton during neurite outgrowth.