Syntaxin 8 Modulates the Post-synthetic Trafficking of the TrkA Receptor and Inflammatory Pain Transmission*

Chen, Bing; Zhao, Ling; Li, Xian; Ji, Yun-Song; Li, Na; Xu, Xufeng; Chen, Zhe-Yu

doi:10.1074/jbc.m114.567925

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…The observed upregulation of syntaxin-8, TMP21, and Munc-18-3 could activate vesicular transport and reparation of injured membranes. Syntaxin-8 (STX8) mediates vesicle docking and fusion with ER, Golgi, and surface membranes [41]. A transmembrane protein TMP21 participates in vesicle trafficking between endoplasmic reticulum and Golgi [42].…”

Section: Discussionmentioning

confidence: 99%

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra. Using the antibody microarrays, we studied changes in expression of >200 neuronal proteins in penumbra 4 or 24 h after focal photothrombotic infarct. Diverse cellular subsystems were involved in the penumbra tissue response: signal transduction pathways such as protein kinase Bα/GSK-3, protein kinase C and its β1 and β2 isoforms, Wnt/β-catenin (axin1, GSK-3, FRAT1), Notch/NUMB, DYRK1A, TDP43; mitochondria quality control (Pink1, parkin, HtrA2); ubiquitin-mediated proteolysis (ubiquilin-1, UCHL1); axon outgrowth and guidance (NAV-3, CRMP2, PKCβ2); vesicular trafficking (syntaxin-8, TMP21, Munc-18-3, synip, ALS2, VILIP1, syntaxin, synaptophysin, synaptotagmin); biosynthesis of neuromediators (tryptophan hydroxylase, monoamine oxidase B, glutamate decarboxylase, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter); intercellular interactions (N-cadherin, PMP22); cytoskeleton (neurofilament 68, neurofilament-M, doublecortin); and other proteins (LRP1, prion protein, β-amyloid). These proteins are involved in neurodegeneration or neuroprotection. Such changes were most expressed 4 h after photothrombotic impact. Immunohistochemical and Western blot studies of expression of monoamine oxidase B, UCHL1, DYRK1A, and Munc-18-3 confirmed the proteomic data. These data provide the integral view on the penumbra response to photothrombotic infarct. Some of these proteins can be potential targets for ischemic stroke therapy.

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Section: Discussionmentioning

confidence: 99%

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

et al. 2016

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“…One such target is the trkA-specific Q-SNARE protein, Syntaxin 8 (STX8). 76 STX8 facilitates trkA receptor transport from the Golgi apparatus to the plasma membrane. Furthermore, knockdown of STX8 in rat DRG resulted in analgesia in models of inflammatory pain and could eventually lead to the generation of additional pain therapeutics.…”

Section: Pharmacotherapymentioning

confidence: 99%

Anti-nerve growth factor in pain management: current evidence

Chang

Hsu

Hottinger

et al. 2016

JPR

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There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established.

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“…STX8 was initially found in the endosomal SNARE complex ( 14 ) but no functional data in any cell type on Stx8 −/− knock-out mice is known to date. It was found to play a role in cystic fibrosis transmembrane conductance regulator trafficking in epithelial cells ( 35 , 36 ), and Golgi-to-plasma membrane trafficking of TrkA receptor in neurons ( 37 ) supporting its role in endosomal trafficking. STX8 was, however, also found on the plasma membrane of PC12 cells ( 38 ) suggesting that its di-leucine-based motif may differentially function in both exocytotic and endocytotic pathways.…”

Section: Discussionmentioning

confidence: 92%

Syntaxin 8 Regulates Platelet Dense Granule Secretion, Aggregation, and Thrombus Stability

Golebiewska

Harper

Williams

et al. 2015

Journal of Biological Chemistry

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Background: The molecular machinery controlling exocytosis of the three secretable granules types in platelets is not fully elucidated.Results: ATP secretion, aggregation, and thrombus stability are defective in Stx8−/− mouse platelets.Conclusion: STX8 is involved in platelet dense granule secretion, and the STX8-mediated pathway contributes to thrombus stabilization.Significance: Identification of the novel functional SNARE STX8 suggests alternative mechanisms of granule secretion exist in platelets.

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Syntaxin 8 Modulates the Post-synthetic Trafficking of the TrkA Receptor and Inflammatory Pain Transmission*

Cited by 20 publications

References 43 publications

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Protein Profile and Morphological Alterations in Penumbra after Focal Photothrombotic Infarction in the Rat Cerebral Cortex

Anti-nerve growth factor in pain management: current evidence

Syntaxin 8 Regulates Platelet Dense Granule Secretion, Aggregation, and Thrombus Stability

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