Syntaxin 12, a Member of the Syntaxin Family Localized to the Endosome

Tang, Bor Luen; Tan, A.; Lim, Lay Kheng; Lee, San San; Low, Delphine Y.H.; Hong, Wanjin

doi:10.1074/jbc.273.12.6944

Cited by 86 publications

(67 citation statements)

References 33 publications

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“…In the case of syntaxin 13, our data are consistent with the published distribution in other cell types (16,27) that have located this SNARE in the tubulovesicular recycling endosome. The distribution of syntaxin 7, in contrast, has been more controversial.…”

Section: Discussionsupporting

confidence: 82%

Syntaxins 13 and 7 Function at Distinct Steps During Phagocytosis

Collins

Schreiber

Grinstein

et al. 2002

The Journal of Immunology

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The phagosome is a dynamic organelle that undergoes progressive changes to acquire the machinery required to kill and degrade internalized foreign particles. This maturation process involves sequential interaction of newly formed phagosomes with several components of the endocytic pathway. The proteins that mediate the ordered fusion of endosomes and lysosomes with the phagosome are not known. In this study, we investigated the possible role of syntaxins present in the endo/lysosomal pathway in directing phagosomal maturation. We show that in phagocytic cells syntaxin 13 is localized to the recycling endosome compartment, while syntaxin 7 is found in late endosomes/lysosomes. Both proteins are recruited to the phagosome, but syntaxin 13 is acquired earlier and rapidly recycles off the phagosome, while syntaxin 7 is recruited later and continues to accumulate throughout the maturation process. Overexpression of truncated (cytosolic) forms of syntaxin 13 or 7 had no effect on phagocytosis, but exerted an inhibitory effect on phagosomal maturation. These results indicate that syntaxins 13 and 7 are both required for interaction of endosomes and/or lysosomes with the phagosome, but play distinct roles in the maturation process.

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Section: Discussionsupporting

confidence: 82%

Syntaxins 13 and 7 Function at Distinct Steps During Phagocytosis

Collins

Schreiber

Grinstein

et al. 2002

The Journal of Immunology

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“…The first group of syntaxins identified (syntaxins 1-4) are predominantly restricted to the plasma membrane, where they mediate constitutive and regulated vesicle trafficking events at the cell surface (19 -21). In contrast, syntaxins 5, 6, 10, 11, and 16 are localized to different subcompartments within the Golgi apparatus (22-26), whereas syntaxins 7, 12, and 13 are found in the post-Golgi endosomal population (27)(28)(29).Although the mechanisms and protein interaction domains responsible for v-SNARE localization have been investigated, there is less information with regard to the targeting of the syntaxin family of t-SNARE proteins, particularly in mammalian cells. Therefore, to further our understanding of t-SNARE targeting we have examined the functional domains of syntaxin 6, a t-SNARE localized to the TGN (23).…”

mentioning

confidence: 97%

mentioning

confidence: 99%

Functional Cooperation of Two Independent Targeting Domains in Syntaxin 6 Is Required for Its Efficient Localization in thetrans-Golgi Network of 3T3L1 Adipocytes

Watson

Pessin

2000

Journal of Biological Chemistry

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To identify the targeting domains of syntaxin 6 responsible for its localization to the trans-Golgi network (TGN), we examined the subcellular distribution of enhanced green fluorescent protein (EGFP) epitopetagged syntaxin 6/syntaxin 4 chimerae and syntaxin 6 truncation/deletion mutants in 3T3L1 adipocytes. Expression of EGFP-syntaxin 6 resulted in a perinuclear distribution identical to endogenous syntaxin 6 as determined both by confocal fluorescence microscopy and subcellular fractionation. Furthermore, both the endogenous and the expressed EGFP-syntaxin 6 fusion protein were localized to a brefeldin A-insensitive but okadaic acid-sensitive compartment characteristic of the TGN. In contrast, EGFP-syntaxin 6 constructs lacking the H2 domain were excluded from the TGN and were instead primarily localized to the plasma membrane. Although syntaxin 4 was localized to the plasma membrane, syntaxin 6/syntaxin 4 chimerae and syntaxin 6 truncations containing the H2 domain of syntaxin 6 were predominantly directed to the TGN. Importantly, the syntaxin 6 H2 domain fused to the transmembrane domain of syntaxin 4 was also localized to the TGN, demonstrating that the H2 domain was sufficient to confer TGN localization. In addition to the H2 domain, a tyrosine-based plasma membrane internalization signal (YGRL) was identified between the H1 and H2 domains of syntaxin 6. Deletion of this sequence resulted in the accumulation of the EGFP-syntaxin 6 reporter construct at the plasma membrane. Together, these data demonstrate that syntaxin 6 utilizes two distinct domains to drive its specific subcellular localization to the TGN.Eukaryotic cells maintain an array of distinct membrane compartments, each outfitted with a unique collection of integral membrane proteins. These compartments serve multiple functions including the organized delivery of proteins to various intracellular destinations, a process accomplished largely through vesicular trafficking events (1-4). Despite the tremendous membrane lipid and protein flux through these intracellular trafficking nodes, many proteins show a remarkably stable, compartment-specific distribution under steady state conditions. Since membrane proteins are thought to be transported vectorially along the secretory pathway, a given protein may transiently occupy several compartments en route to its final destination. Indeed, delivery of proteins to various intracellular destinations may in some cases require a series of sorting decisions. One critical sorting step occurs at the transGolgi network (TGN), 1 where proteins with specific targeting signals are incorporated into vesicles with defined trafficking itineraries (5-7). In addition, retrieval signals are often employed to return wayward proteins back to their resident membrane compartments (8 -12). In contrast, membrane proteins without specific sorting signals are transported along the entire secretory pathway and accumulate at the plasma membrane under steady-state conditions (13).Our understanding of vesicular trafficking is largel...

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“…VAMP3 was targeted because of its observed colocalization with MMP2 and MMP9 (Fig. 1); syntaxin-13 (also known as syntaxin-12) was targeted because it is known to interact with SNAP23 (Tang et al, 1998) and with SNAP25, a neuronal homolog of SNAP 23 (Aikawa et al, 2006). We generated mutant forms of these SNAREs lacking transmembrane domains (VAMP3cyto and Syn13cyto).…”

Section: Snare Constructs Bind Specifically To Endogenous Snares In Hmentioning

confidence: 99%

VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion

Kean

Williams

Skalski

et al. 2009

Journal of Cell Science

102

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evidence that SNAREs contribute to trafficking of MMPs. Syntaxin-4 (Miyata et al., 2004) and Ti-VAMP (tetanus-insensitive vesicleassociated membrane protein, also known as VAMP7) (Steffen et al., 2008) have been shown to be involved in cellular invasion and trafficking of MT1-MMP. SNAP25 (synaptosome-associated protein of 25 kDa) has been found to partly colocalize with MMP7 in epithelial cells (Gorodeski, 2007). There is also recent evidence that directly links SNARE-mediated intracellular membrane traffic to cell-ECM interactions (Al-Awar et al., 2000;Roberts et al., 2001). We (Gonon et al., 2005;Skalski and Coppolino, 2005;Tayeb et al., 2005), along with others (Proux-Gillardeaux et al., 2005), have reported that SNARE-mediated trafficking, including that mediated by the plasma membrane SNARE SNAP23 and the endosomal SNARE VAMP3, is required for cell adhesion and migration in cultured mammalian cell systems.In the present study, we examined the roles that SNAP23, VAMP3 and syntaxin-13 play in the secretion of MMPs and the degradation of ECM by HT-1080 fibrosarcoma cells. We report that SNAP23 and VAMP3 are required for secretion of MMP2 and MMP9, and that these SNAREs and syntaxin-13 are involved in trafficking of the membrane-bound MT1-MMP to the cell surface. Inhibiting the function of SNAP23, VAMP3 or syntaxin-13 using dominantnegative mutants of the SNAREs, RNA interference (RNAi) or tetanus toxin impaired the in situ degradation of gelatin by the cells. We present data that are the first to show that VAMP3, syntaxin-13 and SNAP23 are required for efficient invasion by HT-1080 cells in vitro. The impaired ECM degradation and reduced invasive capacity observed in cells as a consequence of inhibiting SNARE function suggests an important role for SNARE-mediated traffic in tumor progression. Results GFP-tagged SNAREs partly overlap with endogenous MMP2 and MMP9 in HT-1080 cellsMMP2 and MMP9 are secreted proteinases that have been shown to contribute to tumor-cell invasion and metastasis. Having identified roles for SNAP23 (Gonon et al., 2005) and VAMP3 (Proux-Gillardeaux et al., 2005;Skalski and Coppolino, 2005;Tayeb et al., 2005) in the non-invasive motility of cells, we sought to investigate the involvement of these SNAREs in the trafficking and secretion of MMPs during cell invasion. SNAP23 is a plasma membrane SNARE found in many cell types, and VAMP3 is a known binding partner of SNAP23 (Hepp et al., 1999). To study MMP activity during cell invasion, we used the human cell line HT-1080, which is derived from a highly invasive fibrosarcoma and is known to express MMP2 and MMP9 along with MT1-MMP (Ginestra et al., 1997;Stanton et al., 1998). The subcellular distributions of endogenous MMP2 and MMP9 were compared with those of GFP-SNAP23 and GFP-VAMP3, and it was observed that SNAP23 ( Fig. 1A) and VAMP3 (Fig. 1B) partly colocalized with both MMP2 and MMP9 at the periphery of HT-1080 cells in response to treatment of the cells with the tumor promoter PMA (phorbol 12-myristate 13-acetate). PMA was added to...

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Syntaxin 12, a Member of the Syntaxin Family Localized to the Endosome

Cited by 86 publications

References 33 publications

Syntaxins 13 and 7 Function at Distinct Steps During Phagocytosis

Syntaxins 13 and 7 Function at Distinct Steps During Phagocytosis

Functional Cooperation of Two Independent Targeting Domains in Syntaxin 6 Is Required for Its Efficient Localization in thetrans-Golgi Network of 3T3L1 Adipocytes

VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion

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