General secretory pathway

Pugsley, A. (1993). The complete general secretory pathway in gram-negative bacteria. Microbiol. Rev. 57, 50-108. 

Thanassi, D. G., Saulino, E. T., and Hultgren, S.J. (1998). The chaperone/usher pathway a major terminal branch of the general secretory pathway. Curr. Opin. Microbiol. 1, 223-231. 

Other Non-Catalytic Domains. Many polysaccharide depolymerizing enzymes are secreted by bacteria and fungi from their intracellular site of synthesis across the periplasmic space and cell wall into the surroundings. These exported enzymes reach their destination via the general secretory pathway [246] which involves membrane protein complexes such as the bacterial ABC transporters [247] that recognize domains on the secreted proteins. There are several examples of non-catalytic domains on microbial carbohydrases that may play a role in transport from the cells. These include a repeat domain on a chitinase involved... 

They are usually synthesized as small precursor proteins or peptides that are processed with proteolytic elimination of their Af-terminal leader sequences, and the resultant mature peptides form one, two, or more putative amphipathic transmembrane a-helical spanners (TMSs). Many bacteriocins are encoded in operons that also encode an immunity protein and an ABC transport system (TC 3.A.l) with a protease domain at the Af-terminus. The ABC systems export the bacteriocins while the protease domains cleave the A-terminal leader sequence. A few bacteriocins are exported by the type II general secretory pathway rather than by ABC-type export systems. In some cases, expression of the bacteriocin-encoding operon is induced by a bacteriocin-like peptide which acts in conjunction with a two component sensor kinase-response regulator. 

Proteins produced in plant cells can remain within the cell or are secreted into the apoplast via the bulk transport (secretory) pathway. In whole plants, because levels of protein accumulated intracellularly, e. g. using the KDEL sequence to ensure retention in the endoplasmic reticulum, are often higher than when the product is secreted [58], foreign proteins are generally not directed for secretion. However, as protein purification from plant biomass is potentially much more difficult and expensive than protein recovery from culture medium, protein secretion is considered an advantage in tissue culture systems. For economic harvesting from the medium, the protein should be stable once secreted and should accumulate to high levels in the extracellular environment. 

About 10-20% of all transmembrane proteins that are targeted to the ER and subsequently enter the secretory pathway are subject to post-translational modification with glycosylphosphatidyl-inositol (GPI). Proteins bearing the GPI anchor are involved in signal transduction, immune response, cancer cell invasion, and metastasis and the pathobiology of trypanosomal parasites. The structure of the GPI anchor has been analyzed for mammals, protozoa, and yeast. The general structure of the glycolipid structure is shown in Scheme 4. 

Of the drug that is administered in eye-drops, 80% diffuses into the general circulation and can have systemic effects, even when low concentrations are used (1). The lacrimal pump is the essential route of diffusion from eye-drops into the systemic circulation, through active cellular absorption in the lacrimal secretory pathways. The active ingredient avoids first-pass metabohsm and reaches its site of action directly, resulting in increased systemic availability. All the same, this form of treatment is generally very well tolerated, when one bears in mind the immense volume of eye-drops prescribed by ophthalmologists each day. 

Fig. 2. Schematic representation of tests using exogenous ACTH, dbcAMP and pregnenolone (indicated by black horizontal arrows) of the functional integrity of teleost adrenocortical cells exposed to an adrenotoxicant (TOX). A lack of secretory response to ACTH (pattern A, black vertical arrow with X to show disrupted pathways) indicates a general dysfunction of the secretory pathways, possibly involving the ACTH receptor. No response to ACTH but a secretory response to dbcAMP, an analog of cAMP (pattern B), indicates that the steps downstream from cAMP are functional (white arrow bar) but steps upstream are disrupted by the toxicant. No response to ACTH or dbcAMP with a response to pregnenolone (pattern C) indicates that steps downstream from this precursor of cortisol are functional. Note that the concentrations of ACTH, dbcAMP and pregnenolone used in these functional in vitro tests should be physiological rather than pharmacological.

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