Membrane proteins, subcellular localization

The intracellular environment may contain individual proteins at concentrations in the milligram-per-milliliter range (Srere, 1967, 1970 Segel, 1975). Considering that the number of different proteins within cells is in the thousands, the total protein concentration must be in the neighborhood of 100 mg/ml (Segel, 1975). Under such conditions, there may take place many protein-protein interactions which cannot be duplicated in in vitro studies. Such interactions undoubtedly play a role in membrane function, subcellular localization of enzyme activity, and membrane transport in cellular membranes. Multienzyme complexes, enzyme polymerization, and specific interactions that engender specialized catalytic functions not present in the isolated enzyme are other phenomena which depend upon protein-protein interactions. 

Cytoplasmically localized protein tyrosine phosphatases have a catalytic domain and other structural elements that specify the subcellular localization and association with effector molecules. These structural elements contain sequence signals for nuclear localization, for membrane association and for association with the cytoskeleton (see Fig. 8.16). The presence of SH2 domains suggests that these molecules might interact with signaling pathways involving growth hormones and receptor tyrosine kinases. 

Several proteins, with binding activities for thyroid hormones, have been detected in a variety of cell types and with different subcellular localizations, i.e., in the plasma membrane, the sarcoplasmic reticulum, the cytosol, the mitochondria and... 

The original experiments on PDI activity were carried out with microsomal membranes, suggesting the localization of this protein in the endoplasmic reticulum. This has since been conhrmed both by subcellular localization studies (Lambert and Freedman, 1985) and by immunochemical methods (Koch, 1987). However, these studies revealed that PDI does not behave like a typical ER membrane protein. Indeed, for some time there was a question as to whether there was more than one form of PDI due to the presence of this protein in the cytosol. This has now been discounted by studies on the latency of PDI that show that if microsomes are prepared carefully then the activity is entirely latent (Lambert and Freedman, 1985). Thus, although PDI exists as an ER protein, it is easily released from microsomes by freeze thawing, mild alkaline treatment, detergents, or sonication, suggesting that PDI is either a soluble protein or is only loosely associated with the ER membrane. 

Two recent reports revealed additional layers of complexity regarding the mechanisms involved in the distinct durations of action associated with the different toxin serotypes. Femandez-Salas et al. (2004) investigated the subcellular localization of BoNT/A, /B, and /E LC-GFP fusion proteins following overexpression in several different mammalian cell lines. The LC/A fusion protein was shown to localize within discrete plasma membrane... 

Berman cl, Yeo EL, Wencel-Drake JD, Furie BC, Ginsberg MH, Furie B. a platelet alphagranuie membrane protein Ih is associated with the plasma membrane after activation characterization and subcellular localization ofidateletacdvation-dependera granule-external membrane proteia7C/in/nvest 78 130-137,1986. 

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