A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum

Schamel, Wolfgang W. A.; Kuppig, Stephan; Becker, Bernd; Gimborn, Kerstin; Hauri, Hans‐Peter; Reth, Michael

doi:10.1073/pnas.1633363100

Cited by 87 publications

(76 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…11 ), we observed some cleavage of BAP31 associated with mitochondria (results not shown). BAP31 is an abundant protein of ER and Golgi membranes 28 that facilitates the retention of proteins within early secretory organelles 29,30 and has been reported to be cleaved by caspase-8. 13 However, BAP31 cleavage was limited and did not extend to all membrane fractions, thereby reducing the possibility of its direct involvement in the traffic alteration observed here.…”

Section: Resultsmentioning

confidence: 99%

“…35 For instance, Fas signalling may impact on secretory routes linking ER with proximal Golgi by early modification of BAP31 13 or similar traffic regulators that retain selected membrane proteins within the ER. 29 Functional alteration of these ER retention proteins via caspase cleavage could induce a dispersal and surface exposure of specific membrane proteins, 29,30 that may include glycoproteins reacting with HPA. 36 Our finding that inhibition of (predominantly) caspase-8 prevents early dispersal of Golgi membranes provides a novel dimension to the early action of apical caspases, especially in type II cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Death receptor ligation triggers membrane scrambling between Golgi and mitochondria

Ouasti

Matarrese²,

Paddon

et al. 2006

Cell Death Differ

View full text Add to dashboard Cite

Subcellular organelles such as mitochondria, endoplasmic reticulum (ER) and the Golgi complex are involved in the progression of the cell death programme. We report here that soon after ligation of Fas (CD95/Apo1) in type II cells, elements of the Golgi complex intermix with mitochondria. This mixing follows centrifugal dispersal of secretory membranes and reflects a global alteration of membrane traffic. Activation of apical caspases is instrumental for promoting the dispersal of secretory organelles, since caspase inhibition blocks the outward movement of Golgi-related endomembranes and reduces their mixing with mitochondria. Caspase inhibition also blocks the FasL-induced secretion of intracellular proteases from lysosomal compartments, outlining a novel aspect of death receptor signalling via apical caspases. Thus, our work unveils that Fas ligand-mediated apoptosis induces scrambling of mitochondrial and secretory organelles via a global alteration of membrane traffic that is modulated by apical caspases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Death receptor ligation triggers membrane scrambling between Golgi and mitochondria

Ouasti

Matarrese²,

Paddon

et al. 2006

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…33,34 These results indicate that accumulation of mutant ␣1ATZ in the ER results in activation of the caspase cascade via both the ER and mitochondrial pathways. For another, we found (unpublished observations) that accumulation of ␣1ATZ in the ER specifically mediated the cleavage/activation of BAP31, an integral membrane protein of the ER that is involved in the ER retention of several proteins 35 and appears to mediate pro-apoptotic signals from the ER to mitochondria. 36 This last result may provide a mechanistic explanation for the mitochondrial dysfunction that was recently found in cell line and transgenic mouse models of ␣1AT deficiency as well as in the liver of deficient patients.…”

Section: Cellular Response Pathways Activated By Er Retention Of ␣1atzmentioning

confidence: 94%

Alpha-1-Antitrypsin Deficiency: A New Paradigm for Hepatocellular Carcinoma in Genetic Liver Disease *

2005

View full text Add to dashboard Cite

Liver disease in alpha-1-antitrypsin (␣1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated. Recent investigations suggest that a specific repertoire of signaling pathways are involved, including the autophagic response, mitochondrial-and ER-caspase activation, and nuclear factor kappaB (NF B) activation. Whether activation of these signaling pathways, presumably to protect the cell, inadvertently contributes to liver injury or perhaps protects the cell from one injury and, in so doing, predisposes it to another type of injury, such as hepatocarcinogenesis, is not yet known. Recent studies also suggest that hepatocytes with marked accumulation of ␣1ATZ, globule-containing hepatocytes, engender a cancer-prone state by surviving with intrinsic damage and by chronically stimulating in 'trans' adjacent relatively undamaged hepatocytes that have a selective T he classic form of alpha-1-antitrypsin (␣1AT) deficiency, associated with homozygosity for the ␣1ATZ allele, is the most common genetic cause of liver disease in children. It also causes chronic liver injury and hepatocellular carcinoma in adults. 1 Moreover, the predilection for hepatocellular carcinoma in homozygotes for the Z allele is significantly greater than that attributable to cirrhosis alone. 1 The histopathological hallmark of the disease is intracellular globules in hepatocytes that stain positively with periodic acid-Schiff (PAS) after treatment with diastase, the so-called PAS-positive/ diastase-resistant globules. Early studies showed that these globules represent the mutant glycoprotein, ␣1ATZ, retained in the rough endoplasmic reticulum (ER) of liver cells (reviewed in Perlmutter 2 ). Although considerable discussion of these globules is found in the literature as well as investigation of their origin, relatively limited discussion, or investigation, has taken place, regarding the curious fact that many hepatocytes in these patients do not have globules (Fig. 1). Studies of the Z#2 mouse model, generated by using a human ␣1ATZ genomic fragment as transgene, 3 have shown that these globuledevoid cells occupy an increasing proportion of the liver as the animal ages and ultimately become the site of adenomas and carcinomas. 4 In more recent studies using the PiZ mouse model, another transgenic mouse created with a human ␣1ATZ genomic fragment, 5 we have shown that there is increased proliferation of these globule-devoid hepatocytes at a rate that is directly proportional to the number of globule-containing hepatocytes. 6

show abstract

“…Bap31 and its homologue Bap29 were originally discovered as B cell receptor-associated proteins (Kim et al, 1994). Although solid evidence demonstrated that Bap31 is involved in apoptosis (Breckenridge et al, 2003), accumulating evidence suggest that Bap31 in healthy cells functions as a cargo receptor for ER export of transmembrane proteins, such as cellubrevin, class I major histocompatibility complex (MHC) molecules, CFTR, membrane-bound immunoglobulin (Ig)G, tetraspanins, cytochrome P450 2C2, and the leukocyte integrin CD11b/CD18, some of which are well-known ERAD substrates (Annaert et al, 1997;Spiliotis et al, 2000;Lambert et al, 2001;Schamel et al, 2003;Paquet et al, 2004;Zen et al, 2004;Stojanovic et al, 2005;Ladasky et al, 2006; SzczesnaSkorupa and Kemper, 2006).In the present study, we show that Bap31 is a component of the ER quality control compartment and that it cycles between the peripheral ER and a juxtanuclear ER or an ER-related compartment along microtubule tracks. …”

mentioning

confidence: 99%

Bap31 Is an Itinerant Protein That Moves between the Peripheral Endoplasmic Reticulum (ER) and a Juxtanuclear Compartment Related to ER-associated Degradation

Wakana

Takai

Nakajima

et al. 2008

MBoC

Self Cite

102

View full text Add to dashboard Cite

Certain endoplasmic reticulum (ER)-associated degradation (ERAD) substrates with transmembrane domains are segregated from other ER proteins and sorted into a juxtanuclear subcompartment, known as the ER quality control compartment. Bap31 is an ER protein with three transmembrane domains, and it is assumed to be a cargo receptor for ER export of some transmembrane proteins, especially those prone to ERAD. Here, we show that Bap31 is a component of the ER quality control compartment and that it moves between the peripheral ER and a juxtanuclear ER or ER-related compartment distinct from the conventional ER-Golgi intermediate compartment. The third and second transmembrane domains of Bap31 are principally responsible for the movement to and recycling from the juxtanuclear region, respectively. This cycling was blocked by depolymerization of microtubules and disruption of dynein-dynactin function. Overexpression of Sar1p and Arf1 mutants affected Bap31 cycling, suggesting that this cycling pathway is related to the conventional vesicular transport pathways. INTRODUCTIONThe endoplasmic reticulum (ER) exhibits a reticular tubular network that extends from the nucleus to the cell periphery along microtubule tracks. It performs a variety of functions, including the synthesis, posttranslational modifications, quality control, and export of secretory and membrane proteins; the synthesis of lipids; stress response; Ca 2ϩ storage; and apoptosis. Most, if not all, of these functions are managed by subdomains, such as the rough and smooth ER and transitional ER sites. Each subdomain contains a unique set of proteins that are responsible for its function and organization. ER subdomains are relatively stable, but they can be transformed into alternative structures in response to cellular conditions (for review, see Voeltz et al., 2002;Levine and Rabouille, 2005;Borgese et al., 2006;Vedrenne and Hauri, 2006).Several studies showed the presence of a specialized ER subdomain that is related to ER-associated degradation (ERAD). ERAD is part of a quality control system that ensures the delivery of only correctly folded or assembled secretory and membrane proteins to their final destinations. Newly synthesized proteins that fail to fold or assemble correctly are retained in the ER, retrotranslocated to the cytosol, and degraded by the ubiquitin-proteasome system (for review, see Ellgaard and Helenius, 2003;Meusser et al., 2005;Rö misch, 2005). Studies using mammalian cells demonstrated that transmembrane ERAD substrates are segregated into "ER quality control compartments," which become discernible at the juxtanuclear region upon inhibition of ERAD by proteasome inhibitors (Kamhi-Nesher et al., 2001;Spiliotis et al., 2002). In Saccharomyces cerevisiae, ectopically expressed cystic fibrosis transmembrane conductance regulator (CFTR) is segregated from other ER proteins and accumulates in ER-associated compartments (Kiser et al., 2001;Zhang et al., 2001;Huyer et al., 2004). Degradation of CFTR in yeast is independent of ER-to-Golgi tr...

show abstract

A high-molecular-weight complex of membrane proteins BAP29/BAP31 is involved in the retention of membrane-bound IgD in the endoplasmic reticulum

Cited by 87 publications

References 49 publications

Death receptor ligation triggers membrane scrambling between Golgi and mitochondria

Death receptor ligation triggers membrane scrambling between Golgi and mitochondria

Alpha-1-Antitrypsin Deficiency: A New Paradigm for Hepatocellular Carcinoma in Genetic Liver Disease *

Bap31 Is an Itinerant Protein That Moves between the Peripheral Endoplasmic Reticulum (ER) and a Juxtanuclear Compartment Related to ER-associated Degradation

Contact Info

Product

Resources

About