Differential effects of experimental glaucoma on intrinsically photosensitive retinal ganglion cells in mice.

Glaucoma is a group of eye diseases characterized by retinal ganglion cell (RGC) loss and optic nerve damage. Studies, including this study, support that RGCs degenerate and die in a type-specific manner following the disease insult. Here we specifically examined one RGC type, the intrinsically photosensitive retinal ganglion cell (ipRGC), and its associated functional deficits in a mouse model of experimental glaucoma.

RhoC Is an Unexpected Target of RhoGDI2 in Prevention of Lung Colonization of Bladder Cancer.

Unlabelled: RhoGDI2 (ARHGDIB) suppresses metastasis in a variety of cancers but the mechanism is unclear, thus hampering development of human therapeutics. RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) for the Rho family of GTPases thought to primarily bind to Rac1; however, Rac1 activation was not decreased by RhoGDI2 expression in bladder cancer cells. To better understand the GTPase-binding partners for RhoGDI2, a mass spectrometry-based proteomic approach was used in bladder cancer cells.

Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions.

Background: Epithelial tissues depend on intercellular homodimerization of E-cadherin and loss of E-cadherin is central to the epithelial to mesenchymal transition seen in multiple human diseases. Signaling pathways regulate E-cadherin function and cellular distribution via phosphorylation of the cytoplasmic region by kinases such as casein kinases but the protein phosphatases involved have not been identified.

Results: This study shows protein Ser/Thr phosphatase-6 catalytic subunit (PP6c) is expressed in epithelial tissue and its mRNA and protein are robustly up-regulated in epithelial cell lines at high vs.

The RacGAP β2-Chimaerin selectively mediates axonal pruning in the hippocampus.

Axon pruning and synapse elimination promote neural connectivity and synaptic plasticity. Stereotyped pruning of axons that originate in the hippocampal dentate gyrus (DG) and extend along the infrapyramidal tract (IPT) occurs during postnatal murine development by neurite retraction and resembles axon repulsion. The chemorepellent Sema3F is required for IPT axon pruning, dendritic spine remodeling, and repulsion of DG axons.

The faces and friends of RhoGDI2.

RhoGDI2 is a guanine nucleotide dissociation inhibitor (GDI) specific for the Rho family of small GTPases that plays dual opposite roles in tumor progression, being both a promoter in tissues such as breast and a metastasis suppressor in tissues such as the bladder. Despite a clear role for this protein in modulating the invasive and metastatic process, the mechanisms through which RhoGDI2 executes these functions remain unclear. This review will highlight the current state of our knowledge regarding how RhoGDI2 functions in metastasis with a focus on bladder cancer and will also seek to highlight other potential underappreciated avenues through which this protein may affect cancer cell behavior.

A novel cross-talk in diacylglycerol signaling: the Rac-GAP beta2-chimaerin is negatively regulated by protein kinase Cdelta-mediated phosphorylation.

Although the family of chimaerin Rac-GAPs has recently gained significant attention for their involvement in development, cancer, and neuritogenesis, little is known about their molecular regulation. Chimaerins are activated by the lipid second messenger diacylglycerol via their C1 domain upon activation of tyrosine kinase receptors, thereby restricting the magnitude of Rac signaling in a receptor-regulated manner. Here we identified a novel regulatory mechanism for beta2-chimaerin via phosphorylation.

Protein kinase C and other diacylglycerol effectors in cancer.

Almost three decades after the discovery of protein kinase C (PKC), we still have only a partial understanding of how this family of serine/threonine kinases is involved in tumour promotion. PKC isozymes - effectors of diacylglycerol (DAG) and the main targets of phorbol-ester tumour promoters - have important roles in cell-cycle regulation, cellular survival, malignant transformation and apoptosis. How do PKC isozymes regulate these diverse cellular processes and what are their contributions to carcinogenesis? Moreover, what is the contribution of all phorbol-ester effectors, which include PKCs and small G-protein regulators? We now face the challenge of dissecting the relative contribution of each DAG signal to cancer progression.

PKC isozymes and diacylglycerol-regulated proteins as effectors of growth factor receptors.

Growth factors exert their cellular effects through signal transduction pathways that are initiated by the ligation of growth factors to their cell surface receptors. One of the well-established effectors of growth factor receptors is protein kinase C (PKC), a family of serine-threonine kinases that have been known for years as the main target of the phorbol ester tumor promoters. While there is abundant information regarding downstream PKC effectors and partners, how individual PKC isozymes become activated by growth factors and the regulation of receptor function by PKCs is only partially understood.

Oligonucleotide microarray for the study of functional gene diversity in the nitrogen cycle in the environment.

The analysis of functional diversity and its dynamics in the environment is essential for understanding the microbial ecology and biogeochemistry of aquatic systems. Here we describe the development and optimization of a DNA microarray method for the detection and quantification of functional genes in the environment and report on their preliminary application to the study of the denitrification gene nirS in the Choptank River-Chesapeake Bay system. Intergenic and intragenic resolution constraints were determined by an oligonucleotide (70-mer) microarray approach.