A vesicular intermediate in the transport of hepatoma secretory proteins from the rough endoplasmic reticulum to the Golgi complex.

Lodish, Harvey; Kong, N; Hirani, Shirish; Rasmussen, Jim

doi:10.1083/jcb.104.2.221

Cited by 127 publications

(58 citation statements)

References 43 publications

(47 reference statements)

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“…Single amino acid changes in Qa-2 and the CD16 IgG Fc receptor converted a PI-glycanlinked protein to a transmembrane protein and truncation of the hydrophobic domain of PLAP produced a secreted protein, but no other single amino acid changes are known to convert a PI-glycan-linked protein to a secreted protein Lanier, et al ., 1989;Kurosaki and Ravetch, 1989) . This finding raises the possibility that AP found in the serum may be a secreted form of the protein rather than a phospholipase cleavage product of cell surface AP Other mutations in PLAP and DAF that prevent PI-glycan addition result in the accumulation of the mutant protein inside the cell, presumably within the ER or Golgi complex (Cara et al, 1989 ;Micanovic et al, 1990;Lodish, 1988) . The mechanism for retention is not clear, but improper folding of the mutant proteins has been proposed as a possibility.…”

Section: Discussionmentioning

confidence: 99%

Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Lowe

1992

The Journal of Cell Biology

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. Placental alkaline phosphatase (PLAP) is anchored in the plasma membrane by a phosphatidylinositol-glycan moiety (PI-glycan) . PIglycan is added posttranslationally to the nascent peptide chain after the removal of 29 amino acids from the COOH-terminus . The contribution of selected COOH-terminal amino acids to the signal for PIglycan addition was tested by creating a fusion protein with the COOH-terminus of PLAP and a secreted protein and by mutagenesis of specific PLAP 000H-terminal amino acids . The cDNA encoding the COOH-terminus of PLAP was fused in frame to the cDNA for human clotting Factor X and expressed in transfected COS-1 cells. Fusion proteins containing 32 amino acids of the PLAP COON-terminus were modified by PI-glycan addition. Thus, the signal for Pl-glycan modification must reside in these amino acids . Next, the region between the hydrophobic domain and the cleavage site was examined for additional number of proteins are anchored in the plasma membrane by a COOH-terminal glycosyl phosphatidylinositol moiety (PI-g1Ycan) (Ferguson and Williams, 1988) . cDNA sequences for Pl-glycan-anchored proteins predict a typical N112-terminal signal peptide that directs the protein to the ER and a 20-30 amino acid COOH-terminal sequence that is absent in the mature PI-glycan-anchored membrane proteins . The PI-glycan attachment occurs in the ER shortly after the peptide chain is synthesized, presumably with the removal of a COOH-terminal peptide (Doering et al., 1990) . The modified protein is then transported to the plasma membrane.The structural determinants that direct the addition of PIglycan to proteins are only partially understood. Studies of decay-accelerating factor (DAF),I Qa-2, and placental alkaline phosphatase (PLAP) suggest that the signals for PIglycan modification reside in or near the COOH-terminal 1. Abbreviations used in this paper: CRD, cross-reacting determinant ; DAF, decay-accelerating factor ; PLAP, placental alkaline phosphatase ; VSG, variable surface glycoprotein .

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Section: Discussionmentioning

confidence: 99%

Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Lowe

1992

The Journal of Cell Biology

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“…Properly folded and oligomerized proteins are further modified in the Golgi area and vesicular transported to their predestined place, e.g. cell surface or extracellular secretion (Pfeffer and Rothman, 1987;Lodish, 1988). In contrast, ER resident proteins, both luminal ER soluble proteins and transmembrane ER proteins, escape from the default bulk flow transport by the presence of specific retention signals.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Lee

1998

Exp Mol Med

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The T cell antigen receptor-CD3 (TCR/CD3) complex is assembled in the endoplasmic reticulum (ER) of T cells after synthesis of individual chains, and is transported to the cell surface for immune recognition and regulation. Partially assembled or unassembled TCR chains are retained and rapidly degraded in the ER. These processes are strictly regulated in the ER at post-translational level for the maintenance of cellular homeostasis. In order to identify the region responsible for the ER retention and rapid degradation of the TCR chain, number of mutants were engineered and their fates, after synthesis in the ER of the HeLa cells, were investigated. Extensive mutagenic analysis of TCR chain, including changing the charged amino acid residues and two tyrosine residues of the transmembrane region into hydrophobic amino acid residues, did not alter the ER retention and rapid degradation. Soluble TCR chain and cytoplasmic tail truncation mutant were also rapidly degraded in the ER. However, N-glycosylation rate of soluble TCR chain in the ER was significantly increased possibily due to the increased exposure of the N-glycosylation site. These results suggest that the ER retention of TCR chain is mediated through its extracellular and transmembrane-cytoplasmic regions and that the rapid ER degradation can be caused by an exposure of unassembled subregion of TCR chain, either extracellular domain or hydrophobic transmembrane region to the hydrophilic environment (lumen of the ER) rather than by presence of a specific degradation signal.

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“…Although the precise function of GRP78-BiP has not yet been defined, more recently it has been suggested to have a general role in the folding and assembly of proteins in the ER (Gething et al, 1986;Munro and Pelham, 1986;Pelham, 1986), to mark aberrantly folded proteins destined for degradation (Gething et al, 1986;Dorner et al, 1987;Lodish, 1988;, or to aid in solubilizing aggregated proteins during times of stress (Munro and Pelham, 1986). Studies using viral membrane glycoproteins as models have implicated a role for GRP78-BiP in the general folding and assembly of proteins in the exocytic pathway.…”

Section: Introductionmentioning

confidence: 99%

Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

Watowich

Lamb

1992

MBoC

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The endoplasmic reticulum (ER)-localized chaperone protein, GRP78-BiP, is involved in the folding and oligomerization of secreted and membrane proteins, including the simian virus 5 hemagglutinin-neuraminidase (HN) glycoprotein. To understand this interaction better, we have constructed a series of HN mutants in which specific portions of the extracytoplasmic domain have been deleted. Analysis of these mutant polypeptides expressed in CV-1 cells have indicated that GRP78-BiP binds to selective sequences in HN and that there exists more than a single site of interaction. Mutant polypeptides have been characterized that are competent and incompetent for association with GRP78-BiP. These mutants have been used to show that the induction of GRP78-BiP synthesis due to the presence of nonnative protein molecules in the ER is dependent on GRP78-BiP complex formation with its substrates. These studies have implications for the function of the GRP78-BiP protein and the mechanism by which the gene is regulated. INTRODUCTIONThe 78-kDa glucose-regulated/Ig heavy-chain binding protein (GRP78-BiP) is a member of the highly con-

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A vesicular intermediate in the transport of hepatoma secretory proteins from the rough endoplasmic reticulum to the Golgi complex.

Cited by 127 publications

References 43 publications

Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Endoplasmic reticulum retention and degradation of T cell antigen receptor β chain

Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

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