A sequential view of neurotransmitter release

Xu, Zheng; Bobich, Joseph A.

doi:10.1016/s0361-9230(98)00040-9

Cited by 30 publications

(12 citation statements)

References 161 publications

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“…In many cells, regulated exocytosis requires a pool of PtdInsP 2 at the release sites (Zheng and Bobich, 1998). Cholesterol-rich membrane domains may provide a means of compartmentalizing not only such signaling lipids (Pike and Miller, 1998) but perhaps also secretory proteins.…”

Section: Annexins and The Organization Of Membrane Microdomainsmentioning

confidence: 99%

“…However, spontaneous fusion is an energetically unlikely event. Zheng and Bobich (1998) raised the possibility that formation of the SNARE complex in exocytosis would release sufficient energy to overcome the energy barrier between the fusing membranes. In the final stages of exocytosis the formation of a fusion pore was observed.…”

Section: Annexins: Fusogenic or Non-fusogenicmentioning

confidence: 99%

“…However, current models postulate that the fusion pore is formed by protein. Synaptophysin is perhaps the most attractive candidate to fill this role (Zheng and Bobich, 1998).…”

Section: Annexins: Fusogenic or Non-fusogenicmentioning

confidence: 99%

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Annexins and Membrane Fusion

Kubista

Sacre

Moss

Subcellular Biochemistry

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Section: Annexins and The Organization Of Membrane Microdomainsmentioning

confidence: 99%

Section: Annexins: Fusogenic or Non-fusogenicmentioning

confidence: 99%

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Annexins and Membrane Fusion

Kubista

Sacre

Moss

Subcellular Biochemistry

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“…The sequence of events in secretion involves many more proteins that link cellular signals with the actual fusion machinery [36,[46][47][48]. In many instances these other proteins are part of a dynamic network of proteinprotein interactions that affect assembly, stability and disassembly of the SNARE complex [49,50].…”

Section: Snare Proteins and Fusionmentioning

confidence: 99%

SNARE Proteins - From Membranes to Genomes

Linial¹

2001

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Abstract:The function and the organization of eukaryotic cells require directional transport of vesicles between compartments. This sort of membrane flow relies on the presence of docking and fusion machinery. The core of this machinery is a protein complex composed of syntaxin, SNAP-25 and VAMP, collectively termed SNAREs. A correct interaction among SNARE prototypes is essential for fruitful docking and fusion. Analysis of large-scale sequencing projects reveals that each of the SNARE proteins (syntaxin, SNAP-25 and VAMP) is a member of a large protein family that is represented in every eukaryotic genome. The diversity among the three SNARE prototypes allows an enriched combinatorial make-up to meet a wide range of cellular demands for secretion.Herein, we discuss the diversity in SNARE proteins from a genomic perspective. We combine information from large-scale sequence data with structural and functional classifications of SNAREs. Using a sequence-based automated protein classification tool, we expose weak but significant connections among all three SNARE protein clusters. These connections define a local evolutionary network within the protein universe. Genomic data allows us to identify classical SNAREs as well as their remote evolutionary relatives. We focus on the SNARE representatives from human and plant genomes to discuss the source of complexity and specificity for docking and fusion in a eukaryotic cell. How many of the potential SNARE combinations are indeed valid in vivo, and to what extent does each combination specify a biochemical and biophysical unique entity, is yet to be experimentally determined. THE SNARE PROTEINS -PAST AND PRESENTThe process of vesicle trafficking and secretion has been investigated in great detail over the last decade (reviewed by [1][2][3][4][5]). Investigators in the field of secretion seem to have come to a consensus that the fusion event relies on a small number of interacting proteins [2,[6][7][8]. The key proteins in this set are syntaxin, SNAP-25, VAMP and variants thereof. These proteins are collectively known as SNAREs [9]. SNARE is an acronym for SNAP receptor, indicating that these proteins function as receptors for NSF (Nethylmaleimide Sensitive Fusion protein) and SNAPs (Soluble NSF Attachment Protein). Association with SNAPs and NSF forms a fusion particle that is essential for vesicular trafficking among subcellular compartments [10,11]. These receptors are localized to two separate membranes that are to be fused [12]. According to their expected localization, they are divided between those on the vesicular membrane (v-SNARE) and those on the target membrane (t-SNARE). The first set of SNAREs identified from solubilized brain extracts includes VAMP/ synaptobrevin on the synaptic vesicle membrane (v-SNARE) and two t-SNAREs, syntaxin and SNAP-25 (from the plasma membrane).Immediately following the identification of mammalian SNAREs, homologues were found in other organisms [13][14][15][16]. It became clear that all three SNARE prototypes are *Address corres...

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“…[1][2] As a result of extensive investigations during the last 2 decades, the signal transduction mechanism by which synaptic vesicles are formed and subsequently release their transmitters and other contents is fairly well understood. [3][4][5][6][7][8][9] Little is known, however, about the signaling mechanism that triggers the trafficking of vesicles from the cell body to the synaptic terminal. Thus, our objective in this investigation was to characterize this signaling system with the use of hypothalamic and brainstem neurons in primary culture and angiotensin II (ang II) as a neuromodulatory hormone.…”

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confidence: 99%

Obligatory Role of Protein Kinase Cβ and MARCKS in Vesicular Trafficking in Living Neurons

et al. 2002

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Abstract-Neurotransmitter release from neurons involves both vesicular trafficking and subsequent fusion of synaptic vesicles with the plasma membrane. The mechanisms involving the formation and fusion of vesicles that allow the exocytotic release of transmitters are understood well. Little is known, however, about the signaling mechanism involved in the trafficking of vesicles along the neurites. In this study, we used real-time confocal microscopy to search for evidence that vesicular trafficking in neurons requires the activation of protein kinase C␤ (PKC␤) and the myristoylated alanine-rich C kinase substrate (MARCKS) signaling pathway. Dopamine-␤-hydroxylase fused to green fluorescent protein has been used to trace vesicular movement. Angiotensin II, an established neuromodulatory hormone, stimulates translocation of green fluorescent protein-dopamine-␤-hydroxylase vesicles from the cell body to neurites. This translocation was blocked by an antisense oligonucleotide to PKC␤ and MARCKS. Stimulation of PKC by other means, such as phorbol-12-myristate-13-acetate or carbachol, also resulted in the redistribution of fluorescence in a manner similar to that observed for angiotensin II. These observations demonstrate that PKC␤-MARCKS signaling may be a general mechanism for the stimulation of vesicular trafficking in brain neurons. Key Words: oligonucleotides, antisense Ⅲ brain Ⅲ neuroregulators Ⅲ norepinephrine Ⅲ signal transduction B oth evoked and enhanced neuronal release of transmitters involves trafficking of vesicles along neurites after fusion at the synaptic terminal and the release of exocytosis. 1-2 As a result of extensive investigations during the last 2 decades, the signal transduction mechanism by which synaptic vesicles are formed and subsequently release their transmitters and other contents is fairly well understood. [3][4][5][6][7][8][9] Little is known, however, about the signaling mechanism that triggers the trafficking of vesicles from the cell body to the synaptic terminal. Thus, our objective in this investigation was to characterize this signaling system with the use of hypothalamic and brainstem neurons in primary culture and angiotensin II (ang II) as a neuromodulatory hormone. Our rationale for electing to use this experimental system was as follows.(1) Primary neuronal cultures from the hypothalamus and brainstem areas contain approximately 30% catecholaminergic neurons, and they have been used as an excellent in vitro model to elucidate the regulation of norepinephrine (NE) synthesis, release, and uptake in the brain. 7,10 (2) These neurons provide an excellent electrophysiological and biochemical model with which to study the cellular and molecular basis of physiological actions such as sympathetic activity, baroreflexes, and vasopressin secretion. 7,10 -11 (3) Stimulation of the neuronal ang II Type 1 receptor (AT 1 R) results in a pattern of NE neuromodulation similar to that seen in the in vivo situation. [12][13][14] (4) The intracellular signal transduction mechanisms that un...

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A sequential view of neurotransmitter release

Cited by 30 publications

References 161 publications

Annexins and Membrane Fusion

Annexins and Membrane Fusion

SNARE Proteins - From Membranes to Genomes

Obligatory Role of Protein Kinase Cβ and MARCKS in Vesicular Trafficking in Living Neurons

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