Role of glyceraldehyde-3-phosphate dehydrogenase in vesicular transport from Golgi apparatus to endoplasmic reticulum

Bryksin, Anton V.; Laktionov, Petr P.

doi:10.1134/s0006297908060011

Cited by 25 publications

(16 citation statements)

References 52 publications

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“…Among the identified proteins, we focused on one peculiar eukaryotic protein: the Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) annotated by spot number 49 on the 2D gel (Figure 2C) and in Table S1. GAPDH has multiple functions within host cells such as glycolysis and apoptosis [16],[17] More interestingly, GAPDH interacts with the small GTPase Rab 2 to control vesicular retrograde transport between the ER and the Golgi [18]. The presence of GAPDH on the BCV membrane leads us to hypothesise that vesicular retrograde transport may be involved in Brucella replication within the ER.…”

Section: Resultsmentioning

confidence: 99%

The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication

et al. 2009

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The intracellular pathogen Brucella abortus survives and replicates inside host cells within an endoplasmic reticulum (ER)-derived replicative organelle named the “Brucella-containing vacuole” (BCV). Here, we developed a subcellular fractionation method to isolate BCVs and characterize for the first time the protein composition of its replicative niche. After identification of BCV membrane proteins by 2 dimensional (2D) gel electrophoresis and mass spectrometry, we focused on two eukaryotic proteins: the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the small GTPase Rab 2 recruited to the vacuolar membrane of Brucella. These proteins were previously described to localize on vesicular and tubular clusters (VTC) and to regulate the VTC membrane traffic between the endoplasmic reticulum (ER) and the Golgi. Inhibition of either GAPDH or Rab 2 expression by small interfering RNA strongly inhibited B. abortus replication. Consistent with this result, inhibition of other partners of GAPDH and Rab 2, such as COPI and PKC ι, reduced B. abortus replication. Furthermore, blockage of Rab 2 GTPase in a GDP-locked form also inhibited B. abortus replication. Bacteria did not fuse with the ER and instead remained in lysosomal-associated membrane vacuoles. These results reveal an essential role for GAPDH and the small GTPase Rab 2 in B. abortus virulence within host cells.

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Section: Resultsmentioning

confidence: 99%

The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication

et al. 2009

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“…This enzyme is also involved in vesicular transport from the Golgi apparatus to the endoplasmic reticulum (ER) [23], and has Ca 2+ -dependant fusogenic activity in human neutropil [105] and rat brain cytosol (Table 1) [106]. Previous studies demonstrated that fusogenic activity was dependent on Ser-234 [107], and inhibited by the substrate G3P.…”

Section: 0 Gapdh Functional Diversitymentioning

confidence: 99%

“…However, recent research suggests that GAPDH possesses highly diverse, non-glycolytic functions, as its expression and activity are affected by multiple factors. In particular, GAPDH has been reported to bind DNA and RNA[1, 4–6], regulate transcription [7], possess kinase/phosphotransferase activity [8–15], catalyze microtubule formation and polymerization [16–22], facilitate vesicular transport [23], and bind integral membrane ion pumps associated with Ca 2+ release [24, 25], as well as interact with a number of small molecules, including tumor necrosis factor (TNF)-α ribozymes [26], glutathione (GSH) [27, 28], p53 [29–31], and nitric oxide (NO) [32–34]. Additionally, since GAPDH also interacts with disease-associated proteins, like huntingtin [35] and the β-amyloid precursor protein (AβPP) [36].…”

Section: Introductionmentioning

confidence: 99%

Oxidatively Modified Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and Alzheimer's Disease: Many Pathways to Neurodegeneration

Butterfield

Hardas

Lange

2010

JAD

235

185

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Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc., that play important roles in normal and pathologic cell function. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the amyloid-beta protein precursor (AbetaPP). Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer's disease (AD) brain due to oxidative modification. Although oxidative stress and damage is a common phenomenon in the AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. In this review, we examine the many functions of GAPDH with respect to AD brain; in particular, the apparent role(s) of GAPDH in AD-related apoptotic cell death is emphasized.

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“…Recent investigations have begun to illuminate these roles. These include endocytosis and membrane fusion, 17 translational control, 18 nuclear tRNA transport, 19 signaling, 20 pathogen virulence, 21 and cell death. 22 It is not clear how GAPDH can be targeted for these specific functions in the cell, but is believed to involve posttranslational modification of the protein.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of glyceraldehyde‐3‐phosphate dehydrogenase inactivation by tyrosine nitration

Palamalai¹,

Miyagi²

2010

Protein Science

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifaceted protein that is involved in numerous processes including glycolysis, translational silencing, transcriptional regulation of specific genes, and acting as a nitric oxide sensor. The precise mechanism on how GAPDH is targeted to these different roles is unclear but believed to involve specific posttranslational modification to the protein. Numerous studies have demonstrated that GAPDH is a target for tyrosine nitration. However, the site of modification and the molecular consequence have not been defined. Rabbit GAPDH with a reversibly protected catalytic cysteine was nitrated in vitro with tetranitromethane, resulting in complete loss of GAPDH catalytic activity. Nitration was estimated as 0.32 mol of nitrotyrosine residue per mole of GAPDH. Mass spectrometry analysis of nitrated GAPDH indicated that Tyr311 and Tyr317 were the sole sites of nitration. The X-ray crystal structure revealed that the distances between Tyr311 and Tyr317 and the cofactor nicotinamide adenine dinucleotide (NAD 1 ) were less than 7.2 and 3.7 Å , respectively, implying that nitration of these two residues may affect NAD 1 binding. This possibility was assessed using an NAD 1 binding assay, which showed that nitrated GAPDH was incapable of binding NAD 1 . Thus, these results strongly suggest that Tyr311 and Tyr317 nitration prohibits NAD 1 binding, leading to the loss of catalytic activity.

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Role of glyceraldehyde-3-phosphate dehydrogenase in vesicular transport from Golgi apparatus to endoplasmic reticulum

Cited by 25 publications

References 52 publications

The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication

The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication

Oxidatively Modified Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and Alzheimer's Disease: Many Pathways to Neurodegeneration

Mechanism of glyceraldehyde‐3‐phosphate dehydrogenase inactivation by tyrosine nitration

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