Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis

Nagano, Koki; Takeuchi, Hiroshi; Gao, Jing; Mori, Yoshihide; Otani, Takahito; Wang, DaGuang; Hirata, Masato

doi:10.1016/j.biocel.2015.02.013

Cited by 15 publications

(19 citation statements)

References 65 publications

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“…) and Akt may modulate exocytosis by phosphorylating tomosyn (Nagano et al . ), a protein important for exocytosis (Gracheva et al . , ).…”

Section: Discussionmentioning

confidence: 99%

“…There are many signaling pathways, such as ERK/MAPK (Spiegel and Milstien 2003) and Akt (Means et al 2007), associated with S1P3 activation. It is shown that ERK/MAPK may regulate exocytosis by organizing synapsin I distribution (Riganti et al 2016) and Akt may modulate exocytosis by phosphorylating tomosyn (Nagano et al 2015), a protein important for exocytosis (Gracheva et al 2006(Gracheva et al , 2007.…”

Section: S1p Is Not Critical For the Quantal Sizementioning

confidence: 99%

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Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Jiang

Delaney

Zanin

et al. 2019

Journal of Neurochemistry

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Sphingosine‐1‐phosphate (S1P) is an essential bioactive sphingosine lipid involved in many neurological disorders. Sphingosine kinase 1 (SphK1), a key enzyme for S1P production, is concentrated in presynaptic terminals. However, the role of S1P/SphK1 signaling in exocytosis remains elusive. By detecting catecholamine release from single vesicles in chromaffin cells, we show that a dominant negative SphK1 (SphK1DN) reduces the number of amperometric spikes and increases the duration of foot, which reflects release through a fusion pore, implying critical roles for S1P in regulating the rate of exocytosis and fusion pore expansion. Similar phenotypes were observed in chromaffin cells obtained from SphK1 knockout mice compared to those from wild‐type mice. In addition, extracellular S1P treatment increased the number of amperometric spikes, and this increase, in turn, was inhibited by a selective S1P3 receptor blocker, suggesting extracellular S1P may regulate the rate of exocytosis via activation of S1P3. Furthermore, intracellular S1P application induced a decrease in foot duration of amperometric spikes in control cells, indicating intracellular S1P may regulate fusion pore expansion during exocytosis. Taken together, our study represents the first demonstration that S1P regulates exocytosis through distinct mechanisms: extracellular S1P may modulate the rate of exocytosis via activation of S1P receptors while intracellular S1P may directly control fusion pore expansion during exocytosis. Open science badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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“…) and Akt may modulate exocytosis by phosphorylating tomosyn (Nagano et al . ), a protein important for exocytosis (Gracheva et al . , ).…”

Section: Discussionmentioning

confidence: 99%

Section: S1p Is Not Critical For the Quantal Sizementioning

confidence: 99%

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Jiang

Delaney

Zanin

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

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“…Catz and colleagues [42] showed that synaptotagmin-like 1 is phosphorylated by Akt and that phosphorylation regulates membrane binding. Of the remaining 8 proteins, syntaxinbinding protein 5 was recently shown to regulate granule secretion in platelets and endothelial cells [34,35], and phosphorylation by Akt and PKA regulates syntaxin-binding protein 5 interaction with syntaxins [43,44]. RIM proteins are central components of the presynaptic active zone complex, where they organize active zones and regulate docking, priming, and the level of granule release [36].…”

Section: Discussionmentioning

confidence: 99%

Frontline Science: Tumor necrosis factor-α stimulation and priming of human neutrophil granule exocytosis

McLeish

Merchant

Creed

et al. 2017

Journal of Leukocyte Biology

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Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function. A role for p38 MAPK regulation of the actin cytoskeleton was confirmed experimentally. Thirteen phosphoproteins regulated secretory vesicle quantity, formation, or release, 4 of which-Raf1, myristoylated alanine-rich protein kinase C (PKC) substrate (MARCKS), Abelson murine leukemia interactor 1 (ABI1), and myosin VI-were targets of the p38 MAPK pathway. Pharmacologic inhibition of Raf1 reduced stimulated exocytosis of gelatinase granules and priming of specific granule exocytosis. We conclude that differential regulation of exocytosis by TNF-α involves the actin cytoskeleton and is a necessary component for priming of the 2 major neutrophil antimicrobial defense mechanisms: oxygen radical generation and release of toxic granule contents.

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“…In rat neuroblastoma cells, PKA-induced phosphorylation of tomosyn-1 on Ser 724 reduces its binding to STX1, enabling cognate SNARE complex formation (51). Likewise, Akt phosphorylated tomosyn-1 on Ser 783 , which disabled binding to STX4 (63). Conversely, phosphorylation of STX1 by ROCK increased its affinity for tomosyn, thereby inhibiting formation of fusogenic SNARE complexes (46,65).…”

Section: Discussionmentioning

confidence: 99%

Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation

et al. 2018

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Soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family proteins mediate membrane fusion critical for vesicular transport and cellular secretion. Mast cells rely on SNARE-mediated membrane fusion for degranulation stimulated by crosslinking of immunoglobulin E (IgE) bound to the Fcε receptor (FcεRI). We investigated the mechanisms downstream of receptor activation that control degranulation. We found that the SNARE binding protein tomosyn-1 (also known as STXBP5) inhibited FcεRI-stimulated degranulation of mast cells. After mast cell activation, tomosyn-1 was phosphorylated on serine and threonine residues, dissociated from the SNARE protein syntaxin 4 (STX4), and associated with STX3. We identified PKCδ as the major kinase required for tomosyn-1 threonine phosphorylation and for regulation of the interaction with STXs. Incubation with high IgE concentrations increased tomosyn-1 abundance in cultured mast cells. Similarly, in basophils from allergic patients with high amounts of serum IgE, the abundance of tomosyn-1 was increased as compared to that in patients with normal IgE concentrations. Our findings identified tomosyn-1 as an inhibitor of mast cell degranulation that required PKCδ to switch its interaction with STX partners during fusion. We suggest that the IgE-mediated increase in tomosyn-1 abundance in allergic patients may represent a counterregulatory mechanism to limit disease development.

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Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis

Cited by 15 publications

References 65 publications

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Frontline Science: Tumor necrosis factor-α stimulation and priming of human neutrophil granule exocytosis

Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation

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