Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others. Dysfunction of IECs can cause diseases. The development, maintenance, and functions of IECs are strongly influenced by external nutrition, such as amino acids. Amino acids play important roles in regulating the properties and functions of IECs. In this article, we briefly reviewed the current understanding of the roles of amino acids in the regulation of IECs’ properties and functions in physiological state, including in IECs homeostasis (differentiation, proliferation, and renewal), in intestinal epithelial barrier structure and functions, and in immune responses. We also summarized some important findings on the effects of amino acids supplementation (e.g., glutamine and arginine) in restoring IECs’ and intestine functions in some diseased states. These findings will further our understanding of the important roles of amino acids in the homeostasis of IECs and could potentially help identify novel targets and reagents for the therapeutic interventions of diseases associated with dysfunctional IECs.

Dishevelled (Dvl) is an essential protein in the Wnt signaling pathways; it uses its PDZ domain to transduce the Wnt signals from the membrane receptor Frizzled to downstream components. Here, we report identifying a drug-like small molecule compound through structure-based ligand screening and NMR spectroscopy and show the compound to interact at low micromolar affinity with the PDZ domain of Dvl. In a Xenopus testing system, the compound could permeate the cell membrane and block the Wnt signaling pathways. In addition, the compound inhibited Wnt signaling and reduced the levels of apoptosis in the hyaloid vessels of eye. Moreover, this compound also suppressed the growth of prostate cancer PC-3 cells. These biological effects suggest that by blocking the PDZ domain of Dvl, the compound identified in our studies effectively inhibits the Wnt signaling and thus provides a useful tool for studies dissecting the Wnt signaling pathways.

Saliva has become an attractive body fluid for on-site, remote, and real-time monitoring of oral and systemic health. At the same time, the scientific community needs a saliva-centered information platform that keeps pace with the rapid accumulation of new data and knowledge by annotating, refining, and updating the salivary proteome catalog. We developed the Human Salivary Proteome (HSP) Wiki as a public data platform for researching and retrieving custom-curated data and knowledge on the saliva proteome. The HSP Wiki is dynamically compiled and updated based on published saliva proteome studies and up-to-date protein reference records. It integrates a wide range of available information by funneling in data from established external protein, genome, transcriptome, and glycome databases. In addition, the HSP Wiki incorporates data from human disease–related studies. Users can explore the proteome of saliva simply by browsing the database, querying the available data, performing comparisons of data sets, and annotating existing protein entries using a simple, intuitive interface. The annotation process includes both user feedback and curator committee review to ensure the quality and validity of each entry. Here, we present the first overview of features and functions the HSP Wiki offers. As a saliva proteome–centric, publicly accessible database, the HSP Wiki will advance the knowledge of saliva composition and function in health and disease for users across a wide range of disciplines. As a community-based data- and knowledgebase, the HSP Wiki will serve as a worldwide platform to exchange salivary proteome information, inspire novel research ideas, and foster cross-discipline collaborations. The HSP Wiki will pave the way for harnessing the full potential of the salivary proteome for diagnosis, risk prediction, therapy of oral and systemic diseases, and preparedness for emerging infectious diseases. Database URL: https://salivaryproteome.nidcr.nih.gov/

Tetraspanin CD82 suppresses cell migration, tumor invasion, and tumor metastasis. To determine the mechanism by which CD82 inhibits motility, most studies have focused on the cell surface CD82, which forms tetraspanin‐enriched microdomains (TEMs) with other transmembrane proteins, such as integrins. In this study, we found that CD82 undergoes endocytosis and traffics to endosomes and lysosomes. To determine the endocytic mechanism of CD82, we demonstrated that dynamin and clathrin are not essential for CD82 internalization. Depletion or sequestration of sterol in the plasma membrane markedly inhibited the endocytosis of CD82. Despite the demand on Cdc42 activity, CD82 endocytosis is distinct from macropinocytosis and the documented dynaminindependent pinocytosis. As a TEM component, CD82 reorganizes TEMs and lipid rafts by redistributing cholesterol into these membrane microdomains. CD82– containing TEMs are characterized by the cholesterolcontaining microdomains in the extreme light‐ and intermediate‐density fractions. Moreover, the endocytosis of CD82 appears to alleviate CD82‐mediated inhibition of cell migration. Taken together, our studies demonstrate that lipid‐dependent endocytosis drives CD82 trafficking to late endosomes and lysosomes, and CD82 reorganizes TEMs and lipid rafts through redistribution of cholesterol.—Xu, C., Zhang, Y. H., Thangavel, M., Richardson, M. M., Liu, L., Zhou, B., Zheng, Y., Ostrom, R. S., Zhang, X. A. CD82 endocytosis and cholesterol‐dependent reorganization of tetraspanin webs and lipid rafts. FASEB J . 23, 3273–3288 (2009). www.fasebj.org