Tetraspanin proteins have recently emerged as a new class of modulators of various processes involving cell surface receptors, including cell migration and invasion, host immune responses, cell-cell fusion, and viral infection. The book summarises recent advances in the fields of biology in which the role of tetraspanins have been established and also covers the molecular evolution of the tetraspanin superfamily and structural aspects of the organisation of tetraspanin microdomains.

Tetraspanins are small (20-50 kDa) integral membrane proteins with four transmembrane domains that have an intrinsic propensity to associate with other membrane proteins and lipids giving rise to the formation of specific tetraspanin-enriched microdomains (TEMs), also referred to as “The tetraspanin web”. In mammals, the tetraspanin family comprises of 33 different members, with the majority of the members being abundantly expressed in almost all cell types, including leukocytes which are responsible for innate and adaptive immunity as well as in other cells that play pivotal roles in immune responses, such as endothelial or stromal cells. Therefore, through the wide range of specific molecular interactions in which they are engaged, tetraspanins influence many processes of up-most relevance in the development, physiology and pathology of the immune system, including the control of immune cell morphology, signaling, adhesion, migration, invasion, fusion, infections and cancer.

In multicellular organisms, communication between cells involves secretion of proteins that bind to receptors on neighboring cells. While this has been well documented, another mode of intercellular communication has recently become the subject of increasing interest: the release of exosomes. In cancer, tumor exosomes are involved in various aspects of pathogenesis, including proliferation, immunosuppression, and metastasis. Given the ability of exosomes to export unneeded endogenous molecules from cells, these structures hold great potential as anticancer therapeutic agents. They are also being studied as prognostic markers for cancer.

Cancer was thought to originate from alterations in intercellular signaling that resulted in the transformation of cells, their uncontrolled proliferation and metastasis. There is now an increasing body of evidence demonstrating that the surrounding matrix and cell-matrix interactions are also major players in this process. Cells adhere and receive signals from various extracellular matrices via transmembrane receptors, the best known of which are the heterodimeric glycoproteins, integrins.

The study of viruses necessarily involves dissecting the intimate details of cellular pathways. Viruses have often been employed as tools in studying cellular pathways, as was done by early retrovirologists such as Peyton Rous in attempting to understand the mechanism of cellular transformation and oncogenesis. On the other side of the coin, virologists seek to de?ne those cellular elements interacting intimatelywiththeir virus ofinterestinorder to better understand viral replication itself, and in some cases to develop antiviral strategies. It is in the intersection of virology and cell biology that many of us ?nd the most rewarding aspects of our research. When a new discovery yields insights into basic cellular mechanisms and presents new targets for int- vention to ?ght a serious pathogen, the impact can be high and the excitement intense. HIV has been no exception to the rule that viruses reveal many basic aspects of cellular biology. In recent years, in part because of the importance of HIV as a major cause of human suffering, numerous cellular processes have been elucidated through work on processes or proteins of this human retrovirus. The excitement in this ?eld is especially well illustrated by the discovery of new innate means of resisting viral replication, such as the work on APOBEC3G, TRIM5a, and BST-2/ tetherin presented in this volume.

The fact that tumors are composed of both tumor cells and host cells has long been known. These tumor-associated cells include vascular endothelial cells and pe- cytes, as well as inflammatory cells such as neutrophils, monocytes, macrophages, mast cells and eosinophils, and lymphocytes. The tumor cells also interact with stromal cells and with elements of the tissue extracellular matrix. What has been less appreciated is the role that these cells could have in modulating the growth, invasion, and metastasis of the tumor. Early on, the elements of what we now call the tumor microenvironment were considered to be more or less innocent bysta- ers to the role of the tumor cells as they grew and invaded local sites. Today, there is an increased understanding of the critical role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination. This volume represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment in cancer development and progression. Perhaps, the earliest recognition of the role of nonmalignant cells as cancer re- lators was the recognition that lymphocytes can participate in what was termed “immune surveillance” in the 1960s. Our understanding of tumor immunity has improved markedly since then, and there are now successful clinical studies sh- ing the potential use of immune-based therapies in cancer treatment.

Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability provides the latest information on Autism spectrum disorders (ASDs), the lifelong neurodevelopmental disorders that present in early childhood and affect how individuals communicate and relate to others and their surroundings. In addition, three quarters of ASD patients also manifest severe intellectual disability. Though certain genes have been implicated, ASDs remain largely a mystery, and research looking into causes and cellular deficits are crucial for better understanding of neurodevelopmental disorders. Despite the prevalence and insidious nature of this disorder, this book remains to be an extensive resource of information and background on the state of current research in the field. The book serves as a reference for this purpose, and discusses the crucial role synaptic activity plays in proper brain function. In addition, the volume discusses the neurodevelopmental synaptopathies and serves as a resource for scientists and clinicians in all biomedical science specialties. This research has been crucial for recent studies that have provided a rationale for the development of pharmacological agents able to counteract functional synaptic anomalies and potentially ameliorate some ASD symptoms. Introduces the genetic and non-genetic causes of autism and associated intellectual disabilities Describes the genes implicated in autistic spectrum disorders and their function Considers major individual genetic causes of autism, Rett syndrome, Fragile X syndrome, and other autism spectrum disorders, as well as their classification as synaptopathies Presents a thorough discussion of the clinical aspects of multiple neurodevelopmental disorders and the experimental models that exist to study their pathophysiology in vitro and in vivo, including animal models and patient-derived stem cell culture