Tomosyn: a Syntaxin-1–Binding Protein that Forms a Novel Complex in the Neurotransmitter Release Process

Fujita, Yasuyuki; Shirataki, Hiromichi; Sakisaka, Toshiaki; Asakura, Takeshi; Ohya, Takeshi; Kotani, Hirokazu; Yokoyama, Shigekazu; Nishioka, Hideo; Matsuura, Yoshiharu; Mizoguchi, Akira; Scheller, Richard H.; Takai, Yoshimi

doi:10.1016/s0896-6273(00)80472-9

Cited by 272 publications

(358 citation statements)

References 47 publications

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“…In contrast, Scrib has only one human homolog, hScrib, although related proteins include ERBIN, Lano, and Densin-180 (Santoni et al 2002). Lgl has two human homologs, Llgl1 and Llgl2, and a somewhat related protein called Tomosyn is also present (Tomotsune et al 1993;Strand et al 1995;Fujita et al 1998).…”

Section: Do Vertebrate Ntsg Homologs Play a Role In Cancer?mentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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Mammalian epithelial tumors lose polarity as they progress toward malignancy, but whether polarity loss might causally contribute to cancer has remained unclear. In Drosophila, mutations in the "neoplastic tumor suppressor genes" (nTSGs) scribble, discs-large, and lethal giant larvae disrupt polarity of epithelia and neuroblasts, and simultaneously induce extensive overproliferation of these cells, which exhibit malignant-like characteristics. Herein I review what is known about the role of the fly nTSGs in controlling cell polarity and cell proliferation. Incorporating data from mammalian studies, I consider how polarity and proliferation can be coupled, and how disruption of polarity could promote cancer.

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Section: Do Vertebrate Ntsg Homologs Play a Role In Cancer?mentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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“…The brain homogenate (S 2 fraction) was prepared as described by Fujita et al (1998). Ca 2ϩ -dependent syntaxin-1A binding proteins from rat brain were detected using PreScission protease (GE Healthcare, Uppsala, Sweden) as described previously (Ohyama et al, 2002).…”

Section: Identification Of Myosin-vamentioning

confidence: 99%

Myosin-Va Regulates Exocytosis through the Submicromolar Ca²+-dependent Binding of Syntaxin-1A

Watanabe

Nomura

Ohyama

et al. 2005

MBoC

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Myosin-Va is an actin-based processive motor that conveys intracellular cargoes. Synaptic vesicles are one of the most important cargoes for myosin-Va, but the role of mammalian myosin-Va in secretion is less clear than for its yeast homologue, Myo2p. In the current studies, we show that myosin-Va on synaptic vesicles interacts with syntaxin-1A, a t-SNARE involved in exocytosis, at or above 0.3 M Ca 2؉ . Interference with formation of the syntaxin-1A-myosin-Va complex reduces the exocytotic frequency in chromaffin cells. Surprisingly, the syntaxin-1A-binding site was not in the tail of myosin-Va but rather in the neck, a region that contains calmodulin-binding IQ-motifs. Furthermore, we found that syntaxin-1A binding by myosin-Va in the presence of Ca 2؉ depends on the release of calmodulin from the myosin-Va neck, allowing syntaxin-1A to occupy the vacant IQ-motif. Using an anti-myosin-Va neck antibody, which blocks this binding, we demonstrated that the step most important for the antibody's inhibitory activity is the late sustained phase, which is involved in supplying readily releasable vesicles. Our results demonstrate that the interaction between myosin-Va and syntaxin-1A is involved in exocytosis and suggest that the myosin-Va neck contributes not only to the large step size but also to the regulation of exocytosis by Ca 2؉ . INTRODUCTIONMyosin-V, a processive molecular motor, conveys vesicles and other organelles along F-actin (Mercer et al., 1991;Espreafico et al., 1992;Cheney et al., 1993;Reck-Peterson et al., 2000;Vale, 2003). This unconventional myosin is a member of the class-V myosins, which are expressed in all eukaryotic species from yeast to mammals (Reck-Peterson et al., 2000;Matsui, 2003;Vale, 2003). Myosin-V is a dimeric protein (Cheney et al., 1993). Each monomer is composed of a head region, a long neck domain containing six tandem IQ-motifs, and a tail region (Reck-Peterson et al., 2000). The head acts as a plus-end ATPase-dependent molecular motor to move myosin-V along F-actin (Reck-Peterson et al., 2000). The long neck region is thought to act as a lever arm to regulate the motor activity of the head and to maintain the large step size of myosin-V via bound light chains. In higher eukaryotes, the light chains consist mainly of calmodulin (CaM) bound to the IQ-motifs in the neck domain (Cheney et al., 1993;Vale, 2003). In addition, the globular tail of myosin-V interacts with membrane-bound vesicles. In these ways, myosin-V plays a central role in intracellular polarized transport (Reck-Peterson et al., 2000;Matsui, 2003;Vale, 2003).Among the three isoforms of myosin-V in higher vertebrates, myosin-Va is the most abundant, and it is highly enriched in the brain (Espreafico et al., 1992), particularly in the neurons (Tilelli et al., 2003). Several lines of evidence indicate that synaptic vesicles, which undergo the Ca 2ϩ -regulated exocytosis, are one of the most important cargoes for myosin-Va (Prekeris and Terrian, 1997;Bridgman, 1999;Tilelli et al., 2003). In addition, Myo2p, a yeast h...

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“…Tomosyn was identified as a molecule with properties consistent with such a role. Tomosyn was found to interact specifically with Syntaxin1A and in so doing displace Munc18a (18).…”

mentioning

confidence: 97%

Tomosyn Interacts with the t-SNAREs Syntaxin4 and SNAP23 and Plays a Role in Insulin-stimulated GLUT4 Translocation

Widberg

Bryant²,

Girotti³

et al. 2003

Journal of Biological Chemistry

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The Sec1p-like/Munc18 (SM) protein Munc18a binds to the neuronal t-SNARE Syntaxin1A and inhibits SNARE complex assembly. Tomosyn, a cytosolic Syntaxin1A-binding protein, is thought to regulate the interaction between Syntaxin1A and Munc18a, thus acting as a positive regulator of SNARE assembly. In the present study we have investigated the interaction between b-Tomosyn and the adipocyte SNARE complex involving Syntaxin4/SNAP23/VAMP-2 and the SM protein Munc18c, in vitro, and the potential involvement of Tomosyn in regulating the translocation of GLUT4 containing vesicles, in vivo. Tomosyn formed a high affinity ternary complex with Syntaxin4 and SNAP23 that was competitively inhibited by VAMP-2. Using a yeast two-hybrid assay we demonstrate that the VAMP-2-like domain in Tomosyn facilitates the interaction with Syntaxin4. Overexpression of Tomosyn in 3T3-L1 adipocytes inhibited the translocation of green fluorescent protein-GLUT4 to the plasma membrane. The SM protein Munc18c was shown to interact with the Syntaxin4 monomer, Syntaxin4 containing SNARE complexes, and the Syntaxin4/Tomosyn complex. These data suggest that Tomosyn and Munc18c operate at a similar stage of the Syntaxin4 SNARE assembly cycle, which likely primes Syntaxin4 for entry into the ternary SNARE complex.

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Tomosyn: a Syntaxin-1–Binding Protein that Forms a Novel Complex in the Neurotransmitter Release Process

Cited by 272 publications

References 47 publications

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Myosin-Va Regulates Exocytosis through the Submicromolar Ca²+-dependent Binding of Syntaxin-1A

Tomosyn Interacts with the t-SNAREs Syntaxin4 and SNAP23 and Plays a Role in Insulin-stimulated GLUT4 Translocation

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Tomosyn: a Syntaxin-1–Binding Protein that Forms a Novel Complex in the Neurotransmitter Release Process

Cited by 272 publications

References 47 publications

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Myosin-Va Regulates Exocytosis through the Submicromolar Ca2+-dependent Binding of Syntaxin-1A

Tomosyn Interacts with the t-SNAREs Syntaxin4 and SNAP23 and Plays a Role in Insulin-stimulated GLUT4 Translocation

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Myosin-Va Regulates Exocytosis through the Submicromolar Ca²+-dependent Binding of Syntaxin-1A