Subcellular localization of proteins is usually guided by their sorting signals encoded by subsequences of amino acids at the N-terminal or C-terminal ends. These signals are usually composed of a set of physichemically conserved amino acid groups such as the hydrophoblic cores of secretory signal peptides. Using experimentally determined sorting signals, biologists have identified the physiche...

The structural and functional integrity of cytoplasmic organelles is maintained by intracellular mechanisms that sort and target newly synthesized proteins to their appropriate cellular locations. In melanocytic cells, melanin pigment is synthesized in specialized organelles, melanosomes. A family of melanocyte-specific proteins, known as tyrosinase-related proteins that regulate melanin pigmen...

T ARGETING of transmembrane proteins to different compartments of the endocytic and late (postGolgi) secretory pathways is largely dependent upon sorting signals contained within the cytosolic domains of the proteins (reviewed in reference 19, 24). The signals are thought to interact with specific recognition molecules, which are components of the machinery involved in the formation of membrane...

Upon recognition of microbial products, Toll-like receptors (TLRs) recruit distinct combinations of adaptors to induce TLR-specific gene expression. In this issue, Kagan and Medzhitov (2006) demonstrate that the adaptor TIRAP/Mal localizes to the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate (PIP2). This binding recruits a key adaptor MyD88 to TLR4, suggesting that there i...

Prediction of protein sorting signals from the sequence of amino acids has great importance in the field of proteomics today. Recently, the growth of protein databases, combined with machine learning approaches, such as neural networks and hidden Markov models, have made it possible to achieve a level of reliability where practical use in, for example automatic database annotation is feasible. ...

Trafficking of soluble cargo to the vacuole is far from being a closed issue as it can occur by different routes and involve different intermediates. The textbook view of proteins being sorted at the post-Golgi level to the lytic vacuole via the pre-vacuole or to the protein storage vacuole mediated by dense vesicles is now challenged as novel routes are being disclosed and vacuoles with interm...

Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral protein...

Traffic of the integral yeast membrane protein chitin synthase III (Chs3p) from the trans-Golgi network (TGN) to the cell surface and to and from the early endosomes (EE) requires active protein sorting decoded by a number of protein coats. Here we define overlapping signals on Chs3p responsible for sorting in both exocytic and intracellular pathways by the coats exomer and AP-1, respectively. ...