Interaction of mammalian neprilysin with binding protein and calnexin in Schizosaccharomyces pombe

Beaulieu, Hugues; Elagöz, Aram; Crine, Philippe; Rokeach, Luis A.

doi:10.1042/bj3400813

Cited by 12 publications

(3 citation statements)

References 45 publications

(56 reference statements)

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“…activity (Xu et al, 2004). Complex formation between calnexin and unglycosylated substrates has also been found in Schizosaccharomyces pombe after treatment of cells with tunicamycin (Beaulieu et al, 1999) or using naturally unglycosylated rHSA as a model protein (Marechal et al, 2004). In contrast to the results of the present study, raising the level of endogenous calnexin did not enhance secretion of rHSA in Schizosaccharomyces pombe (Marechal et al, 2004).…”

Section: Discussioncontrasting

confidence: 89%

Increase of calnexin gene dosage boosts the secretion of heterologous proteins byHansenula polymorpha

Klabunde¹,

Kleebank²,

Piontek³

et al. 2007

FEMS Yeast Research

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The type I membrane protein calnexin is a conserved key component of the quality control mechanism in the endoplasmic reticulum. It functions as a molecular chaperone that monitors the folding state of nascent polypeptides entering the endoplasmic reticulum. Calnexin also behaves as a lectin, as its chaperoning activity involves binding of oligosaccharide moieties present on newly imported glycoproteins. We isolated the calnexin gene (HpCNE1) from the methylotrophic yeast Hansenula polymorpha, and used HpCNE1 expression plasmids for supertransformation of H. polymorpha strains secreting target proteins of biotechnological interest. The elevated dosage of HpCNE1 enhanced secretion of the four proteins tested: three glycoproteins and one unglycosylated product. Secretion of bacterial alginate epimerase AlgE1 was increased threefold on average, and secretion of both human interferon-γ and fungal consensus phytase twofold. With phytase and AlgE1 this improvement was all the more remarkable, as the secretion level was already high in the original strains (g L−1 range). The same approach improved secretion of human serum albumin, which lacks N-linked glycans, about twofold. Glycosylation of the pro-MFα1 leader may account for the effect of calnexin in this case. Our results argue that cooverexpression of calnexin can serve as a generally applicable tool for enhancing the secretion of all types of heterologous protein by H. polymorpha.

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Section: Discussioncontrasting

confidence: 89%

Increase of calnexin gene dosage boosts the secretion of heterologous proteins byHansenula polymorpha

Klabunde¹,

Kleebank²,

Piontek³

et al. 2007

FEMS Yeast Research

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“…Calnexin is a molecular chaperone that has key roles in protein folding and quality control in the ER, and that is well conserved throughout species (Ellgaard & Frickel, 2003;Schrag et al, 2003;Trombetta & Parodi, 2003;Helenius & Aebi, 2004;Hebert et al, 2005;Lederkremer & Glickman, 2005;van Anken & Braakman, 2005). While calnexin displays selectivity for glycoproteins, it has also been shown to assist the folding of nonglycosylated proteins both in vitro and in vivo (Jannatipour et al, 1998;Beaulieu et al, 1999;Ihara et al, 1999;Saito et al, 1999;Stronge et al, 2001;Maréchal et al, 2004). Structurally, calnexin is a type I membrane-bound protein containing a large luminal domain and a short cytosolic tail.…”

Section: Introductionmentioning

confidence: 99%

The calnexin-independent state does not compensate for all calnexin functions inSchizosaccharomyces pombe

Turcotte

Roux

Beauregard

et al. 2007

FEMS Yeast Research

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In the yeast Schizosaccharomyces pombe, the molecular chaperone calnexin (Cnx1p) has been shown to be essential for viability. However, we recently reported that, under certain circumstances, S. pombe cells are able to survive in the absence of calnexin/Cnx1p, indicating that an inducible pathway can complement the calnexin/Cnx1p essential function(s). This calnexin-independent state (Cin) is transmitted by a nonchromosomal proteinaceous element exhibiting several prion-like properties. To assess to what extent the Cin state compensates for the absence of calnexin/Cnx1p, the Cin strain was further characterized. Cin cells exhibited cell-wall defects, sensitivity to heat shock, as well as higher secretion levels of a model glycoprotein. Together, these results indicate that the Cin state does not compensate for all calnexin/Cnx1p functions. Reintroduction of plasmid-borne cnx1(+) partially rescued most but not all of the phenotypes displayed by Cin cells. Interestingly, Cin cells in stationary phase exhibited increased levels of caspase activation, and this phenotype was not suppressed by the reintroduction of cnx1(+), suggesting that cells in the Cin state are subjected to a stress other than the absence of calnexin/Cnx1p.

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“…NEP is primarily expressed in the kidney, where it has the capacity to cleave and inactivate the natriuretic and vasodilatory peptide (ANP), which controls arterial pressure (Beaulieu et al, 1999). The first physiological function of NEP was found in the brain, where NEP is located in neuronal cells.…”

Section: Neutral Endopeptidasementioning

confidence: 99%

Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes

Macours

Poels

Hens

et al. 2004

International Review of Cytology

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Angiotensin-converting enzyme, a member of the M2 metalloprotease family, and endothelin-converting enzyme, a member of the M13 family, are key components in the regulation of blood pressure and electrolyte balance in mammals. From this point of view, they serve as important drug targets. Recently, the involvement of these enzymes in the development of Alzheimer's disease was discovered. The existence of homologs of these enzymes in invertebrates indicates that these enzyme systems are highly conserved during evolution. Most invertebrates lack a closed circulatory system, which excludes the need for blood pressure regulators. Therefore, these organisms represent excellent targets for gaining new insights and revealing additional physiological roles of these important enzymes. This chapter reviews the structural and functional aspects of ACE and ECE and will particularly focus on these enzyme homologues in invertebrates.

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Interaction of mammalian neprilysin with binding protein and calnexin in Schizosaccharomyces pombe

Cited by 12 publications

References 45 publications

Increase of calnexin gene dosage boosts the secretion of heterologous proteins byHansenula polymorpha

Increase of calnexin gene dosage boosts the secretion of heterologous proteins byHansenula polymorpha

The calnexin-independent state does not compensate for all calnexin functions inSchizosaccharomyces pombe

Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes

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