Syntaxin 16’s Newly Deciphered Roles in Autophagy

Tang, Bor Luen

doi:10.3390/cells8121655

Cited by 13 publications

(12 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results indicated that alcohol upregulates the expression of VAMP3, VAMP5 and VAMP7 and synatxin16 in hepatocytes and increased levels of these SNAREs were also found in ALD patients. VAMP3, VAMP7 and syntaxin16 were shown to mediate fusion between MVBs with autophagosomes and autolysosome formation (Miller and Shindell, 1998;Tang, 2019), and we recently described a link between miR-155 and lysosome dysfunction and exosome production (Babuta et al, 2019). VAMP7 was also demonstrated to participate in the fusion between MVBs with the plasma membrane to release exosomes (Fader et al, 2009).…”

Section: Mirna-192 Regulates the Exosome Secretion Via Targeting Rabs...mentioning

confidence: 99%

See 1 more Smart Citation

Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

Bala

Babuta

Catalano

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Exosomes are membrane vesicles released by various cell types into the extracellular space under different conditions including alcohol exposure. Exosomes are involved in intercellular communication and as mediators of various diseases. Alcohol use causes oxidative stress that promotes exosome secretion. Here, we elucidated the effects of alcohol on exosome biogenesis and secretion using human hepatocytes. We found that alcohol treatment induces the expression of genes involved in various steps of exosome formation. Expression of Rab proteins such as Rab1a, Rab5c, Rab6, Rab10, Rab11, Rab27a and Rab35 were increased at the mRNA level in primary human hepatocytes after alcohol treatment. Rab5, Rab6 and Rab11 showed significant induction in the livers of patients with alcohol-associated liver disease. Further, alcohol treatment also led to the induction of syntenin, vesicle-associated membrane proteins (VAMPs), and syntaxin that all play various roles in exosome biogenesis and secretion. VAMP3, VAMP5, VAPb, and syntaxin16 mRNA transcripts were increased in alcohol treated cells and in the livers of alcohol-associated liver disease (ALD) patients. Induction in these genes was associated with increases in exosome secretion in alcohol treated hepatocytes. We found that hepatocyte enriched miR-192 and miR-122 levels were significantly decreased in alcohol treated hepatocytes whereas their levels were increased in the cell-free supernatant. The primary transcripts of miR-192 and miR-122 were reduced in alcohol treated hepatocytes, suggesting alcohol partially affects these miRNAs at the transcriptional level. We found that miR-192 has putative binding sites for genes involved in exosome secretion. Inhibition of miR-192 in human hepatoma cells caused a significant increase in Rab27a, Rab35, syntaxin7 and syntaxin16 and a concurrent increase in exosome secretion, suggesting miR-192 regulates exosomes release in hepatocytes. Collectively, our results reveal that alcohol modulates Rabs, VAMPs and syntaxins directly and partly via miR-192 to induce exosome machinery and release.

show abstract

Section: Mirna-192 Regulates the Exosome Secretion Via Targeting Rabs...mentioning

confidence: 99%

“…The vSNARE protein, VAMP7 was demonstrated to mediate the fusion of secretory lysosomes with the plasma membrane and to regulate of EVs release (Fader et al, 2009). Syntaxins belong to t-SNAREs proteins and play an important role in membrane trafficking and autophagy (Tang, 2019;Mori et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

Bala

Babuta

Catalano

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Accumulating evidence demonstrates that Syntaxin (Stx)5, Stx17, and Stx16 are involved in the autophagy pathway (Tang, 2019). Stx17 is a SNARE protein mainly localized in the ER and partly in the ERGIC (Muppirala et al, 2011) and is essential for maintaining the architecture of ERGIC and the Golgi (Muppirala et al, 2011), and it contributes to the autophagy pathway at several stages from initiation to maturation (Gu et al, 2019).…”

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

confidence: 99%

“…In addition, Stx17 interacts with mAtg8s via the LIR motif and inserts into the autophagosomal membrane (Kumar et al, 2018;Shen et al, 2020). Stx16 is localized in the late Golgi compartments, receives retrograde transport from the endosomes (Xu et al, 2002), and is involved in autophagy by facilitating the transport of ATG9a-containing vesicles to growing autophagosomes (Tang, 2019). Moreover, stx16 is recruited by Atg8/LC3/GABARAP family proteins to autophagosomes and endolysosomes (Tang, 2019).…”

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

confidence: 99%

“…Stx16 is localized in the late Golgi compartments, receives retrograde transport from the endosomes (Xu et al, 2002), and is involved in autophagy by facilitating the transport of ATG9a-containing vesicles to growing autophagosomes (Tang, 2019). 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).…”

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

confidence: 99%

See 1 more Smart Citation

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

SNAREs and developmental disorders

Tang

2020

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Members of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type‐specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18‐1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18‐2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.

show abstract

Syntaxin 16’s Newly Deciphered Roles in Autophagy

Cited by 13 publications

References 91 publications

Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

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

SNAREs and developmental disorders

Contact Info

Product

Resources

About