The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors.

Adhesion class G protein-coupled receptors (aGPCR) form the second largest group of seven-transmembrane-spanning (7TM) receptors whose molecular layout and function differ from canonical 7TM receptors. Despite their essential roles in immunity, tumorigenesis, and development, the mechanisms of aGPCR activation and signal transduction have remained obscure to date. Here, we use a transgenic assay to define the protein domains required in vivo for the activity of the prototypical aGPCR LAT-1/Latrophilin in Caenorhabditis elegans.

Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse.

Background: Adhesion G protein-coupled receptors (aGPCR) constitute a structurally and functionally diverse class of seven-transmembrane receptor proteins. Although for some of the members important roles in immunology, neurology, as well as developmental biology have been suggested, most receptors have been poorly characterized.

Results: We have studied evolution, expression, and function of an entire receptor group containing four uncharacterized aGPCR: Gpr110, Gpr111, Gpr115, and Gpr116.

The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse.

Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish.

Latrophilin signalling in tissue polarity and morphogenesis.

Understanding the mechanisms that coordinate the polarity of cells and tissues during embryogenesis and morphogenesis is a fundamental problem in developmental biology. We have recently demonstrated that the putative neurotoxin receptor lat-1 defines a mechanism required for the alignment of cell division planes in the early embryo of the nematode C. elegans.

Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo.

Understanding the mechanisms that coordinate the orientation of cell division planes during embryogenesis and morphogenesis is a fundamental problem in developmental biology. Here we show that the orphan receptor lat-1, a homolog of vertebrate latrophilins, plays an essential role in the establishment of tissue polarity in the C. elegans embryo.

The druggable genome: an update.

Annotating the druggable genome estimates the potential maximum size of the playing field for current small-molecule drug design but It does not consider biologicals or future breakthroughs in medicinal chemistry or biology.

Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.

Two seemingly unrelated hallmarks of memory CD8(+) T cells are cytokine-driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8(+) T cells and natural killer cells share cytotoxic potential and dependence on the growth factor interleukin 15. We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8(+) T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming.

Modulation of eomes activity alters the size of the developing heart: implications for in utero cardiac gene therapy.

Congenital heart disease is the most prevalent cause of infant morbidity and mortality in developed countries. The mechanisms responsible for many specific types of congenital cardiac malformations are strongly associated with gene abnormalities. However, at this time no strategies for gene therapy of the various congenital heart malformations have been investigated.

Mutations in dynein link motor neuron degeneration to defects in retrograde transport.

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology.