Elaine Collier

O-linked oligosaccharides on insulin receptor.

The insulin receptor, an integral membrane glycoprotein, is synthesized as a single-chain precursor that is cleaved to produce two mature subunits, both of which contain N-linked oligosaccharide chains and covalently linked fatty acids. We report that the beta-subunit also contains O-linked oligosaccharides. The proreceptor, alpha-subunit, and beta-subunit were labeled with [3H]mannose and [3H]galactose in the presence or absence of an inhibitor of O-linked glycosylation. Tryptic peptides from each component were separated by reverse-phase high-performance liquid chromatography. N- and O-linked oligosaccharide chains were identified on these peptides by specific enzymatic digestions. The proreceptor and alpha-subunit contained only N-linked oligosaccharides, whereas the beta-subunit contained both N- and O-linked oligosaccharides. The O-linked oligosaccharide chains were attached to a single tryptic fraction of the beta-subunit, which also contained N-linked chains. This fraction was further localized to the NH2-terminal tryptic peptide of the beta-subunit by specific immunoprecipitation with an anti-peptide antibody with specificity for this region. Binding of insulin and autophosphorylation of the beta-subunit were not dependent on O-linked glycosylation, because cells grown in the presence of the inhibitor exhibited a normal dose response to insulin. Therefore, the insulin receptor contains O-linked oligosaccharides on the NH2-terminal tryptic peptide of the beta-subunit, and these O-linked oligosaccharides are not necessary to the binding or autophosphorylation function of the receptor.

Chapter 5 Molecules of intercellular communication in vertebrates, invertebrates and microbes: do they share common origins?

Publisher Summary This chapter reviews (1) materials in microbes that resemble vertebrate receptors for hormones and other intercellular messengers, (2) intercellular communication in microbes, and (3) materials that resemble vertebrate hormones in microbes, higher plants, amphibian skin, and very young avian embryos. The term “glandulocentric” is introduced to indicate a traditional approach whereby each hormone is thought to be a unique product of one endocrine gland. Because the typical vertebrate endocrine gland is limited to vertebrates, its hormonal product had been thought to be similarly restricted in distribution. The one-to-one relationship between hormone and gland is similarly applied conceptually to the endocrine system in insects and in mollusks. Intercellular communication is widespread in microbes. In Saccharomyces cerevisiae, the common yeast, there are two sex types—α and A—which communicate one with the other via peptide messengers, designated α factor and A factor. Materials that resemble vertebrate-type messenger peptides are present in plants. The paleocentric approach, which suggests that these messengers originated early in evolution before the divergence of life forms into separate kingdoms, easily accommodates these observations. Many of the messenger peptides of vertebrate as well as their receptors and many of their post-receptor components have their evolutionary origins among the microbes and appear to be distributed among a very wide range of forms of life.

The NIH Science of Behavior Change Program: Transforming the science through a focus on mechanisms of change

The goal of the NIH Science of Behavior Change (SOBC) Common Fund Program is to provide the basis for an experimental medicine approach to behavior change that focuses on identifying and measuring the mechanisms that underlie behavioral patterns we are trying to change. This paper frames the development of the program within a discussion of the substantial disease burden in the U.S. attributable to behavioral factors, and details our strategies for breaking down the disease- and condition-focused silos in the behavior change field to accelerate discovery and translation. These principles serve as the foundation for our vision for a unified science of behavior change at the NIH and in the broader research community.