Stx5-Mediated ER-Golgi Transport in Mammals and Yeast

Linders, Peter T. A.; Horst, Chiel van der; Beest, Martin ter; Bogaart, Geert van den

doi:10.3390/cells8080780

Cited by 45 publications

(72 citation statements)

References 111 publications

(280 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have suggested that movement of GLUT4 from the ERGIC towards the GLUT4-storage compartment plays a key role in the trafficking of newly synthesised GLUT4 in human cells (Camus et al, 2020). The SNARE proteins BET1, BET1L, GOSR1, GOSR2, SEC22A, SEC22B, SEC22C, Stx5 and YKT6 are known to be involved in trafficking to or from the ERGIC (Zhang & Hong, 2001;Appenzeller-Herzog & Hauri, 2006;Adnan et al, 2019;Linders et al, 2019). We therefore examined the effect of knockdown of these SNAREs on the distribution of HA-GLUT4-GFP by examining overlap of GFP with the ERGIC marker ERGIC-53 or the Golgi marker GM130.…”

Section: Identification Of New Components Of Glut4 Traffickingmentioning

confidence: 99%

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Morris

Geoghegan

Sadler

et al. 2020

PeerJ

View full text Add to dashboard Cite

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)-containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells.

show abstract

Section: Identification Of New Components Of Glut4 Traffickingmentioning

confidence: 99%

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Morris

Geoghegan

Sadler

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…2b, c), which forms a complex with Stx5 upon retrograde intra-Golgi trafficking [12][13][14][15] , were also reduced. In contrast, the expression of Qc-SNARE Bet1, which forms a complex with Stx5 upon anterograde ER-Golgi trafficking 5,7,13,26 was not reduced (Fig. 2b, c).…”

Section: Molecular Investigations Results In the Identification Of Varmentioning

confidence: 96%

“…Given that Stx5 mediates ER-Golgi trafficking 2,[4][5][6][7]12,13,15,24,26 , we next investigated whether the glycosylation defect in Stx5M55V patient fibroblasts was caused by the mislocalization of glycosyltransferases. We performed immunofluorescence labeling of mannosyl (α-1,3-)-glycoprotein β-1,2-Nacetylglucosaminyltransferase (MGAT1, also known as GnTI), which catalyzes the addition of GlcNAc to the immature man-5 N-glycan.…”

Section: Stx5m55v Mutation Results In Mislocalization Of Glycosyltranmentioning

confidence: 99%

Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5

Linders

Gerretsen

Ashikov

et al. 2020

Preprint

View full text Add to dashboard Cite

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identified a novel human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Whereas Golgi morphology was unaltered, primary human dermal fibroblasts isolated from these patients showed defective glycosylation and mislocalization of glycosyltransferases. Measurements of anterograde trafficking, based on biotin-synchronizable forms of Stx5 (the RUSH system), and of cognate binding SNAREs, based on Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. This is the first time a mutation in an alternative starting codon is linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.

show abstract

“…Moreover, stx16 is recruited by Atg8/LC3/GABARAP family proteins to autophagosomes and endolysosomes (Tang, 2019). Stx5 is involved in ER-Golgi trafficking of specialized cargo molecules, and its proper expression maintains the normal morphology and function of the Golgi in mammalian cells (Linders et al, 2019). The STX5 partner SNARE GS27 binds to both COG6 and COG8, and the COG complex plays a regulatory role in the cis-Golgi-localized STX5 SNARE complex (Willett et al, 2013).…”

Section: Soluble N-ethylmaleimide-sensitive-factor-attachment Proteinmentioning

confidence: 99%

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Deng

Liu

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Autophagy has dual effects in human diseases: appropriate autophagy may protect cells from stress, while excessive autophagy may cause cell death. Additionally, close interactions exist between autophagy and the Golgi. This review outlines recent advances regarding the role of the Golgi apparatus in autophagy. The signaling processes of autophagy are dependent on the normal function of the Golgi. Specifically, (i) autophagy-related protein 9 is mainly located in the Golgi and forms new autophagosomes in response to stressors; (ii) Golgi fragmentation is induced by Golgirelated proteins and accompanied with autophagy induction; and (iii) the endoplasmic reticulum-Golgi intermediate compartment and the reticular trans-Golgi network play essential roles in autophagosome formation to provide a template for lipidation of microtubule-associated protein 1A/1B-light chain 3 and induce further ubiquitination. Golgi-related proteins regulate formation of autophagosomes, and disrupted formation of autophagy can influence Golgi function. Notably, aberrant autophagy has been demonstrated to be implicated in neurological diseases. Thus, targeted therapies aimed at protecting the Golgi or regulating Golgi proteins might prevent or ameliorate autophagy-related neurological diseases. Further studies are needed to investigate the potential application of Golgi therapy in autophagy-based neurological diseases.

show abstract

Stx5-Mediated ER-Golgi Transport in Mammals and Yeast

Cited by 45 publications

References 111 publications

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Contact Info

Product

Resources

About