Latest research on Adhesion GPCRs has unearthed surprising revelations about the events that govern the signal transduction of these receptor molecules and the cellular and organ requirements for these signals. Unexpected and unprecedented findings suggest that Adhesion GPCRs constitute a group of receptors that sense mechanical stimuli and transcode them into metabotropic signals through the action of a novel activation paradigm. Interdisciplinary efforts transcending many areas of biomedical research including pharmacology, physiology, genetics, cell biology, structural biology, biochemistry and bioinformatics were necessary to unveil these fundamental properties. The scientific leaders in the field that carried this research effort have teamed up here to provide a comprehensive overview of our current understanding, how Adhesion GPCRs signal and how these receptors shape organ structure and function.

Upon completion of the human genome project over 800 G protein-coupled receptor 1 (GPCR) genes, subdivided into five categories, were identified. These receptors sense a diverse array of stimuli, including peptides, ions, lipid analogues, light and odour, in a discriminating fashion. Subsequently, they transduce a signal from the ligand–receptor complex into numerous cellular responses. The importance of GPCRs is further reflected in the fact that they constitute the most common target for therapeutic drugs across a 2 wide range of human disorders. Phylogenetic analysis of GPCRs produced the GRAFS classification system, which subdivides GPCRs into five discrete families: glutamate, rhodopsin, adhesion, frizzled/taste2 and secretin receptors. The adhesion-GPCR family 2 can be further subdivided into eight groups. The field of adhesion-GPCR biology has indeed become large enough to require a volume dedicated solely to this field. The contributors to this book have made a courageous effort to address the key concepts of adhesion-GPCR biology, including the evolution and biochemistry of adhesion-GPCRs; there are extensive discussions on the functional nature of these receptors during development, the immune response and tumourgenesis. Finally, there are chapters dedicated to adhesion-GPCR signalling, an area of intense investigation.

The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.

Many advances have been made in the last decade in the understanding of the computational principles underlying olfactory system functioning. Neuromorphic Olfaction is a collaboration among European researchers who, through NEUROCHEM (Fp7-Grant Agreement Number 216916)-a challenging and innovative European-funded project-introduce novel computing p

G protein-coupled receptors (GPCRs) have emerged as incredibly successful drug targets. Members of the adhesion GPCRs (aGPCR) family are characterized by diverse extracellular regions (ECRs), which play roles in cell adhesion, and mediate a subset of aGPCR functions in vivo. Though these receptors are implicated in myriad disease processes, there are no aGPCR-targeted therapeutics to date, due in large part to both the absence of well-behaving ligands as well as the technical challenges associated with mechanistic studies of aGPCR ECRs. We present a structural and functional study of the aGPCR GPR56/ADGRG1, a receptor critical for neurodevelopment and leukemia progression. To overcome many of the challenges mentioned above, we generated over thirty synthetic protein ligands, termed monobodies, that bind diverse epitopes across the ECR. Using a monobody crystallization chaperone, we solved the structure of the full ECR of GPR56, a first for any aGPCR, revealing the domain boundaries in the ECR as well as the identity and unique fold of the previously undefined N-terminal domain. We showed this domain regulates signaling and natural ligand binding in vitro, is deleted via alternative splicing, and mediates myelination in vivo. Additionally, we developed monobodies with stimulatory and inhibitory functions, demonstrating that ECR-targeted ligands can directly regulate aGPCR signaling, and are therefore valuable experimental reagents as well as lead-molecules for therapeutic development. Our results suggest an intricate, ECR-mediated molecular mechanism underlying aGPCR regulation. With the ultimate goal of combating aGPCR-mediated diseases, our findings will pave the way for targeted therapeutic development.