Synovial sarcomas are aggressive tumors of adolescent and young adults that account for up to 10% of soft tissue sarcomas. Cytogenetically, they are characterized by translocation t(X;18), which is found in more than 95% of tumors. In most cases, it results in fusion of the SYT gene with the SSX1 or SSX2 gene, thus creating SYT-SSX1 or SYT-SSX2 rearrangement. The 2 types of gene fusion have bee...

Ca(2+) influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca(2+) in triggering vesicle fusion though the Ca(2+) sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca(2+) influx remain unclear. In this study, we demonstrate that fusion-competent Syt 4 vesicles locali...

Synaptotagmins (Syts) are a group of type I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. All Syts possess a single transmembrane domain, and two conserved tandem Ca(2+)-binding C2 domains. However, Syts IV and XI possess a conserved serine in their C2A domain that precludes these Syts from binding Ca(2+) and phospholipids, and from...

This study demonstrates deregulation of polycomb activity by the synovial sarcoma-associated SYT-SSX2 oncogene, also known as SS18-SSX2. Synovial sarcoma is a soft tissue cancer associated with a recurrent t(X:18) translocation event that generates one of two fusion proteins, SYT-SSX1 or SYT-SSX2. The role of the translocation products in this disease is poorly understood. We present evidence t...

UNLABELLED Synovial sarcoma is an aggressive soft-tissue malignancy of children and young adults, with no effective systemic therapies. Its specific oncogene, SYT-SSX (SS18-SSX), drives sarcoma initiation and development. The exact mechanism of SYT-SSX oncogenic function remains unknown. In an SYT-SSX2 transgenic model, we show that a constitutive Wnt/β-catenin signal is aberrantly activated by...

Tucker, and Edwin Chapman (University of Wisconsin, Madison, WI) find that PIP 2 is a plasma membrane dock for synaptotagmin-1 (syt), a transmembrane protein localized in secretory vesicle membranes, when calcium is absent. This dock may ensure speedy and directed fusion in response to calcium influx. The syt dock has two calcium-binding domains in its cytoplasmic region, called C 2 A and C 2 B...

The synaptic vesicle protein synaptotagmin I (syt) promotes exocytosis via its ability to penetrate membranes in response to binding Ca(2+) and through direct interactions with SNARE proteins. However, studies using full-length (FL) membrane-embedded syt in reconstituted fusion assays have yielded conflicting results, including a lack of effect, or even inhibition of fusion, by Ca(2+). In this ...

We have identified a new human gene coined sytdep (synaptotagmin XIV-derived protein) in human neutrophils. Sytdep encodes a 188-amino acid sequence with a 21.435kDa deduced molecular mass, showing 75% identity to human synaptotagmin (syt) XIV. Human neutrophils express sytdep, but not syt XIV. Sytdep was upregulated during HL-60 neutrophil differentiation. Sytdep gene is located in human chrom...

Tucker, and Edwin Chapman (University of Wisconsin, Madison, WI) find that PIP 2 is a plasma membrane dock for synaptotagmin-1 (syt), a transmembrane protein localized in secretory vesicle membranes, when calcium is absent. This dock may ensure speedy and directed fusion in response to calcium influx. The syt dock has two calcium-binding domains in its cytoplasmic region, called C 2 A and C 2 B...

Synaptic vesicle fusion at many synapses has been kinetically separated into two distinct Ca(2+)-dependent temporal components consisting of a rapid synchronous phase followed by a slower asynchronous component. Mutations in the synaptic vesicle Ca(2+) sensor Synaptotagmin 1 (Syt 1) reduce synchronous neurotransmission while enhancing the slower asynchronous phase of release. Syt 1 regulation o...