Functional properties of multiple synaptotagmins in brain

Ullrich, Bernd; Cai, Li; Zhang, Jimmy Z.; McMahon, Harvey T.; Anderson, Richard G. W.; Geppert, Martin; Südhof, Thomas C.

doi:10.1016/0896-6273(94)90415-4

Cited by 189 publications

(218 citation statements)

References 26 publications

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“…Syts are assumed to be vesicle proteins. However, vesicular localization has previously been demonstrated only for Syts I, 11, 111, and V (Perin et al, 1990;Ullrich et al, 1994;Hudson and Birnbaum, 1995). Syt I has been localized to both small synaptic vesicles (Matthew et al,198 1) and large dense-core vesicles (Walch-Solimena et al, 1993).…”

Section: Subcellular Localization Of Syt IV Protein In Pc12 Cellsmentioning

confidence: 98%

“…For example, the Syt IV C2A domain, in contrast to the C2A domains of many other Syts, is unable to bind calcium or phospholipid (Ullrich et al, 1994;von Poser et al, 1997). The C2B domain and carboxy-terminal 30 amino acids of Syt IV mediate Ca2+-independent binding to the AP-2 protein (Ullrich et al, 1994) and the plasma membrane protein neurexin, respectively (Perin, 1996).…”

Section: G D Ferguson Et Almentioning

confidence: 99%

“…To date, 11 Syt isoforms have been identified (Perin et al, 1990;Li et al, 1995;Babity et al, 1997;von Poser et al, 1997) and several have been demonstrated to be synaptic vesicle proteins (Perin et al, 1990;Ullrich et al, 1994;Hudson and Birnbaum, 1995). Syts are characterized by an intravesicular amino terminus, a short transmembrane domain, and a cytosolic region comprised of two structurally similar, but functionally distinct, C2 domains.…”

mentioning

confidence: 99%

“…Disruption of the murine Syt I gene or the Syt genes of Drosophila (DiAntonio et al, 1993) or Caenorhabditis elegans (Nonet et al, 1993) significantly impairs evoked, Ca2+-dependent synaptic neurotransmitter release. Syt I1 and Syt 111, based on their tissue distribution and biochemical properties, may also function in evoked neurotransmitter release (Ullrich et al, 1994). Thus, Syts appear to play a major role as Ca2+ sensors that couple neuronal excitation to Ca2+-dependent secretion.…”

mentioning

confidence: 99%

“…For example, all Syts tested to date bind the clathrin-adaptor protein AP-2 with high affinity (Ullrich et al, 1994;Zhang et al, 1994). As synaptic vesicles are thought to recycle through endosomes via clathrin-coated pits (Rindler, 1992;Siidhof, 1995), Syts may also function as AP-2 receptors that participate in assembly of the clathrin lattice.…”

mentioning

confidence: 99%

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Synthesis, Degradation, and Subcellular Localization of Synaptotagmin IV, a Neuronal Immediate Early Gene Product

Ferguson¹,

Thomas²,

Elferink³

et al. 1999

Journal of Neurochemistry

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Synaptotagmin IV (Syt Iv) is an immediate early gene induced by depolarization in rat PC12 cells and in rat hippocampus. We prepared an antiserum to Syt IV protein. The 46-kDa Syt IV protein is nearly undetectable by western blotting in unstimulated PC12 cells. After depolarization, Syt IV increases rapidly, peaks at 4 h, and decays to near baseline levels by 12 h. Forskolin stimulation also leads to rapid Syt IV protein accumulation. The rate of Sfl IV protein synthesis, determined by labeling with radioactive amino acids and immunoprecipitation, is low in unstimulated PC12 cells, but increases over the first 3 h after forskolin stimulation and remains elevated for several hours. Syt IV protein is relatively labile; metabolically labeled Syt IV has a half-life of -2 h in PC12 cells. Sucrose density gradient fractionation and vesicle immunoisolation experiments suggest that Syt IV protein is present in both synaptic-like microvesicles and secretory granules. Vesicles immunoisolated from forskolintreated PC12 cells with anti-Syt I antibody contain radioactively labeled Syt IV, demonstrating that Syt I and Syt IV colocalize in common vesicles. These results suggest that Syt IV protein, after its stimulation-induced synthesis, is rapidly transported to secretory vesicles where it may transiently modulate the exocytotic machinery.

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Section: Subcellular Localization Of Syt IV Protein In Pc12 Cellsmentioning

confidence: 98%

Section: G D Ferguson Et Almentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis, Degradation, and Subcellular Localization of Synaptotagmin IV, a Neuronal Immediate Early Gene Product

Ferguson¹,

Thomas²,

Elferink³

et al. 1999

Journal of Neurochemistry

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C 2‐Domain Proteins Involved in Membrane Traffic

Rizo

2004

Handbook of Metalloproteins

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C 2 ‐domains are the second‐most abundant Ca 2+ ‐binding modules in nature. Their most common activity is Ca 2+ ‐dependent phospholipid binding, but other types of interactions have been observed for these versatile protein modules. A variety of proteins involved in membrane traffic contain multiple C 2 ‐domains, which often appear as two tandem C 2 ‐domains as in the case of synaptotagmins and rabphilin. The structures of the C 2 ‐domains of these proteins consist of a conserved β‐sandwich, formed by two four‐stranded β‐sheets, with variable loops at the top and the bottom that sometimes contain α‐helices. Multiple Ca 2+ ‐ions bind in a tight cluster at the top loops, usually without inducing substantial conformational changes. Instead, electrostatic changes caused by Ca 2+ binding induce the Ca 2+ ‐dependent interactions of C 2 ‐domains, which can also be aided by hydrophobic interactions and partial coordination of Ca 2+ by the target molecules. Extensive analysis of the structure and Ca 2+ ‐binding properties of the two synaptotagmin 1 C 2 ‐domains has helped design genetic experiments that have strongly supported the notion that this protein acts as the major Ca 2+ sensor in neurotransmitter release. These studies have also suggested that Ca 2+ ‐dependent phospholipid binding underlies the function of synaptotagmin 1 in triggering release.

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C 2‐Domain Proteins Involved in Membrane Traffic

Rizo¹

2004

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Functional properties of multiple synaptotagmins in brain

Cited by 189 publications

References 26 publications

Synthesis, Degradation, and Subcellular Localization of Synaptotagmin IV, a Neuronal Immediate Early Gene Product

Synthesis, Degradation, and Subcellular Localization of Synaptotagmin IV, a Neuronal Immediate Early Gene Product

C 2‐Domain Proteins Involved in Membrane Traffic

C 2‐Domain Proteins Involved in Membrane Traffic

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