The long-term goal of the project is to identify the molecular signals which direct membrane proteins to specific locations in the cell or to the cell surface. The mechanisms which govern membrane protein assembly and sorting are crucial to the maintenance of intracellular organization and cellular interactions. Four specific projects are planned, and all will employ recombinant DNA technology to analyze membrane protein structure and transport. 1) Available evidence indicates that the cytoplasmic domains of transmembrane glycoproteins can influence their transport to the cell surface. To test the generality of cytoplasmic domains as signals in membrane protein sorting, expression and mutagenesis of two genes encoding glycoproteins targeted to intracellular membranes (Golgi and nuclear) are proposed. 2) To determine if cytoplasmic domains can redirect proteins from one membrane to another, exchanging of cytoplasmic domains among membrane proteins targeted to the plasma membrane, the Golgi apparatus membranes, and the nuclear membrane is proposed. 3) To determine if proteins which are normally secreted can be anchored on the cell surface, a membrane anchor sequence and cytoplasmic domain from a protein transported to the cell surface will be attached to rat growth hormone, a protein which is normally secreted. 4) To determine if proteins which are normally cytoplasmic can be secreted or anchored at the cell surface, a signal sequence or signal and anchor sequences will be fused to cytoplasmic proteins.
| Zagouras, P; Rose, J K (1989) Carboxy-terminal SEKDEL sequences retard but do not retain two secretory proteins in the endoplasmic reticulum. J Cell Biol 109:2633-40 |
| Pitta, A M; Rose, J K; Machamer, C E (1989) A single-amino-acid substitution eliminates the stringent carbohydrate requirement for intracellular transport of a viral glycoprotein. J Virol 63:3801-9 |
| Guan, J L; Ruusala, A; Cao, H et al. (1988) Effects of altered cytoplasmic domains on transport of the vesicular stomatitis virus glycoprotein are transferable to other proteins. Mol Cell Biol 8:2869-74 |
| Fukuda, M; Guan, J L; Rose, J K (1988) A membrane-anchored form but not the secretory form of human chorionic gonadotropin-alpha chain acquires polylactosaminoglycan. J Biol Chem 263:5314-8 |
| Shaw, A S; Rottier, P J; Rose, J K (1988) Evidence for the loop model of signal-sequence insertion into the endoplasmic reticulum. Proc Natl Acad Sci U S A 85:7592-6 |
