Kinectin-dependent Assembly of Translation Elongation Factor-1 Complex on Endoplasmic Reticulum Regulates Protein Synthesis

Ong, Lawrence; Lin, Pao-Chun; Zhang, Xin; Chia, Ser-Mien; Yu, Hanry

doi:10.1074/jbc.m607555200

Cited by 27 publications

(32 citation statements)

References 68 publications

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“…Assembly of EF-1 into ER is important for regulating protein synthesis in eukaryotic cells. Kinectin is the major membrane anchor for EF-1 complex into ER (Ong et al 2006). Indeed, the kinectin-dependent anchorage of EF-1 into ER regulates the efficiency of membrane and cytosolic protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of NME1/NDPK A null mouse liver: evidence for a post-translational regulation of annexin IV and EF-1Bα

Bruneel

Wendum

Labas

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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NME/NDPK family proteins are involved in the control of intracellular nucleotide homeostasis as well as in both physiological and pathological cellular processes, such as proliferation, differentiation, development, apoptosis, and metastasis dissemination, through mechanisms still largely unknown. One family member, NME1/NDPK-A, is a metastasis suppressor, yet the primary physiological functions of this protein are still missing. The purpose of this study was to identify new NME1/NDPK-A-dependent biological functions and pathways regulated by this gene in the liver. We analyzed the proteomes of wild-type and transgenic NME1-null mouse livers by combining two-dimensional gel electrophoresis and mass spectrometry (matrix-assisted laser desorption/ionization time of flight and liquid chromatography-tandem mass spectrometry). We found that the levels of three proteins, namely, phenylalanine hydroxylase, annexin IV, and elongation factor 1 Bα (EF-1Bα), were strongly reduced in the cytosolic fraction of NME1(-/-) mouse livers when compared to the wild type. This was confirmed by immunoblotting analysis. No concomitant reduction in the corresponding messenger RNAs or of total protein level was observed, however, suggesting that NME1 controls annexin IV and EF-1Bα amounts by post-translational mechanisms. NME1 deletion induced a change in the subcellular location of annexin IV in hepatocytes resulting in enrichment of this protein at the plasma membrane. We also observed a redistribution of EF-1Bα in NME1(-/-) hepatocytes to an intracytoplasmic compartment that colocalized with a marker of the reticulum endoplasmic. Finally, we found reduced expression of annexin IV coincident with decreased NME1 expression in a panel of different carcinoma cell lines. Taken together, our data suggest for the first time that NME1 might regulate the subcellular trafficking of annexin IV and EF-1Bα. The potential role of these proteins in metastatic dissemination is discussed.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of NME1/NDPK A null mouse liver: evidence for a post-translational regulation of annexin IV and EF-1Bα

Bruneel

Wendum

Labas

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The recruitment of ER, a major protein synthesis machinery, to FAs might be important for localised translation by actively translating the localised mRNAs of transmembrane FA proteins such as integrins (Adereth et al, 2005). In cultured cells, immunofluorescence studies of the protein elongation eEF1B complex, exhibits an ER-like intracellular distribution associated with kinectin (Ong et al, 2006;Sanders et al, 1996). Hence, the role of the eEF1B complex is intimately associated with ER dynamics.…”

Section: Discussionmentioning

confidence: 99%

Kinectin-mediated endoplasmic reticulum dynamics supports focal adhesion growth in the cellular lamella

Zhang

Tee

Heng

et al. 2010

Journal of Cell Science

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SummaryFocal adhesions (FAs) control cell shape and motility, which are important processes that underlie a wide range of physiological functions. FA dynamics is regulated by cytoskeleton, motor proteins and small GTPases. Kinectin is an integral endoplasmic reticulum (ER) membrane protein that extends the ER along microtubules. Here, we investigated the influence of the ER on FA dynamics within the cellular lamella by disrupting the kinectin-kinesin interaction by overexpressing the minimal kinectin-kinesin interaction domain on kinectin in cells. This perturbation resulted in a morphological change to a rounded cell shape and reduced cell spreading and migration. Immunofluorescence and live-cell imaging demonstrated a kinectin-dependent ER extension into the cellular lamella and ER colocalisation with FAs within the cellular lamella. FRAP experiments showed that ER contact with FAs was accompanied with an increase in FA protein recruitment to FAs. Disruption of the kinectin-kinesin interaction caused a reduction in FA protein recruitment to FAs. This suggests that the ER supports FA growth within the cellular lamella. Microtubule targeting to FAs is known to promote adhesion disassembly; however, ER contact increased FA size even in the presence of microtubules. Our results suggest a scenario whereby kinectin-kinesin interaction facilitates ER transport along microtubules to support FA growth.

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“…and X.O.B., unpublished data and ref. 59). Cytoskeletal elements are also critical in movement of vesicles between the ER and Golgi (60,61).…”

Section: Discussionmentioning

confidence: 99%

Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells

Hewett

Tannous

Niland

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

132

135

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TorsinA is an AAA ؉ protein located predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope responsible for early onset torsion dystonia (DYT1). Most cases of this dominantly inherited movement disorder are caused by deletion of a glutamic acid in the carboxyl terminal region of torsinA. We used a sensitive reporter, Gaussia luciferase (Gluc) to evaluate the role of torsinA in processing proteins through the ER. In primary fibroblasts from controls and DYT1 patients most Gluc activity (95%) was released into the media and processed through the secretory pathway, as confirmed by inhibition with brefeldinA and nocodazole. Fusion of Gluc to a fluorescent protein revealed coalignment and fractionation with ER proteins and association of Gluc with torsinA. Notably, fibroblasts from DYT1 patients were found to secrete markedly less Gluc activity as compared with control fibroblasts. This decrease in processing of Gluc in DYT1 cells appear to arise, at least in part, from a loss of torsinA activity, because mouse embryonic fibroblasts lacking torsinA also had reduced secretion as compared with control cells. These studies demonstrate the exquisite sensitivity of this reporter system for quantitation of processing through the secretory pathway and support a role for torsinA as an ER chaperone protein.early onset dystonia ͉ endoplasmic reticulum ͉ luciferase ͉ protein translation

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Kinectin-dependent Assembly of Translation Elongation Factor-1 Complex on Endoplasmic Reticulum Regulates Protein Synthesis

Cited by 27 publications

References 68 publications

Proteomic analysis of NME1/NDPK A null mouse liver: evidence for a post-translational regulation of annexin IV and EF-1Bα

Proteomic analysis of NME1/NDPK A null mouse liver: evidence for a post-translational regulation of annexin IV and EF-1Bα

Kinectin-mediated endoplasmic reticulum dynamics supports focal adhesion growth in the cellular lamella

Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells

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