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Cited by 305

The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.

The Endoplasmic Reticulum—Gateway of the Secretory Pathway

Open access
Vitale, Alessandro, Denecke, Jürgen·1999·The Plant Cell
DOI 10.1105/tpc.11.4.615
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Abstract

In the mid to late 1960s, the discovery that eukaryotic secreted proteins are first segregated in the lumen of the endoplasmic reticulum (ER) before traveling within membranous structures to reach the cell surface placed the ER at the start point of a newly recognized metabolic pathway now known as the secretory pathway (Palade, 1975). In a review based mainly on observations of plant cells, Morré and Mollenhauer (1974) posited the endomembrane system as the functional integration of the ER, Golgi complex, secretory vesicles, plasma membrane, and hydrolytic compartments (vacuoles in plants and lysosomes in animals). A number of intermediate compartments have been identified more recently (see Battey et al., 1999; Marty, 1999; Sanderfoot and Raikhel, 1999, in this issue). In the secretory pathway, proteins travel from the ER through the Golgi apparatus to arrive at the cell surface or at vacuoles. This biosynthetic, or anterograde, traffic is balanced by retrograde traffic running in the opposite direction. The retrograde traffic allows for endocytosis of extracellular molecules as well as recycling of membranes and proteins to maintain the integrity of the different compartments. Routes from the ER to vacuoles, bypassing the Golgi complex, also exist (Levanony et al., 1992; Robinson et al., 1995; Hara-Nishimura et al., 1998; Jiang and Rogers, 1998; see Sanderfoot and Raikhel, 1999, in this issue). Protein trafficking in the secretory pathway can occur both via vesicle budding with subsequent fusion and via passage along connecting tubules. The lumens of the ER, Golgi complex, and vacuole are topologically equivalent to the cell exterior, and extracellular domains of plasma membrane proteins are thus lumenal when they start their journey in the ER. Because nearly all eukaryotic proteins are synthesized in the cytosol, those destined to reside in a different location must cross membranes in an unfolded state and then fold and assemble in the compartment of destination. However, the mechanisms of traffic along the secretory pathway involve only a single translocation event across the ER membrane, after which proteins do not have to cross any further membrane to reach other stations along the pathway. The ER is therefore unique among the compartments of the eukaryotic cell. It takes care of the folding and assembly not only of its own residents but also of proteins destined to other locations. The crucial role of the ER in safeguarding the correct folding and assembly of proteins has become clearer in the past two decades with the discovery of the ER molecular chaperone machinery and the associated quality control mechanisms (the term “quality control” was introduced in a review by Hurtley and Helenius, 1989). These safeguards not only optimize folding and assembly of newly synthesized secretory proteins but also dispose of defective ones (Haas and Wabl, 1983; Munro and Pelham, 1986; Hammond et al., 1994; Wiertz et al., 1996; Pedrazzini et al., 1997). Secretory proteins usually enter the ER cotranslationally. Translocation of soluble proteins depends on the N-terminal signal peptide. Integral membrane proteins may also be synthesized with an N-terminal signal peptide, but their orientation within the ER membrane and the translocation of portions that will eventually reside in the lumen are determined by the corresponding membrane-spanning domains. The N-terminal signal peptide is removed cotranslationally while the nascent polypeptide is emerging into the ER lumen (Vitale et al., 1993). Removal is performed by signal peptidase, an enzyme located on the lumenal surface of the ER membrane. For many years, translocation across the ER membrane was thought to occur directly through the membrane itself by virtue of the hydrophobic core of the signal peptide. Studies with fluorescently labeled proteins, however, have shown that polypeptides remain in an aqueous environment during translocation (Crowley et al., 1993). Thus, the current model of protein translocation involves a multiprotein pore, termed the translocon pore, with an aqueous channel of 9 to 15 Å in diameter when inactive and 40 to 60 Å when operational (Hamman et al., 1998). The growing polypeptide emerges on the lumenal side of the membrane and begins to fold in the ER lumen. If the protein contains a as do many membrane proteins, then translocation is and the hydrophobic into the membrane to become domains. The current model not for protein translocation but the as to the of the ER is in of the in its membrane. however, a to for the of the ER membrane. in the lumenal protein the lumenal of the inactive when is in protein the is on the side by the and is from the lumenal side (Crowley et al., et al., 1998). The of the ER which from that of the cytosol, is thus at all and molecular that reside in the ER have been identified and have been termed are in compartment in which protein folding and assembly occur in to proteins that are to molecular to of and as

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Metadata

Authors
Vitale, A., & Denecke, J.
Venue
The Plant Cell
Publisher
Oxford University Press (OUP)
Published
1999-04
Volume
11
Issue
4
Pages
615-628
ISSN
  • 1040-4651 (ISSN-L)
  • 1532-298X
DOI
10.1105/tpc.11.4.615
OpenAlex
W2128700764
Cited by
305
References
69
FWCI
6.34
Type
journal article
Language
en
Open access
bronze

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