Proteins Involved in Synaptic Vesicle Docking and Fusion

Burns, Marie E.; Beushausen, Sven; Chin, Gilbert; Tang, Deman; DeBello, William M.; Dresbach, Thomas; O’Connor, Vincent; Schweizer, Felix E.; Wang, S. S H; Whiteheart, Sidney W.; Hawkey, L.A.; Betz, Heinrich; Augustine, G. J.

doi:10.1101/sqb.1995.060.01.038

Cited by 4 publications

(3 citation statements)

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“…Indeed, Rabphilin-3A is the most active reagent among the >50 that we have injected into the squid giant presynaptic terminal ( Burns et al, 1996 ). Although squid Rabphilin-3A has not yet been identified, squid presynaptic proteins typically are highly homologous to their mammalian counterparts ( Bommert et al, 1993 ; Hunt et al, 1994 ; DeBello et al, 1995 ; Burns et al, 1996 ; O'Connor et al, 1997 ; Dresbach et al, 1998 ). Thus, there is strong reason to suspect that Rabphilin-3A is present in squid presynaptic terminals and has a primary sequence homologous to the mammalian protein that we have injected.…”

Section: Discussionmentioning

confidence: 99%

“…We have found that bovine Rabphilin-3A and its fragments potently inhibit neurotransmitter release when microinjected into the presynaptic terminal of squid. Indeed, Rabphilin-3A is the most active reagent among the Ͼ50 that we have injected into the squid giant presynaptic terminal (Burns et al, 1996). Although squid Rabphilin-3A has not yet been identified, squid presynaptic proteins typically are highly homologous to their mammalian counterparts (Bommert et al, 1993;Hunt et al, 1994;DeBello et al, 1995;Burns et al, 1996;O'Connor et al, 1997;Dresbach et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

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Rabphilin-3A: A Multifunctional Regulator of Synaptic Vesicle Traffic

Burns

Sasaki

Takai

et al. 1998

The Journal of General Physiology

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103

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We have investigated the function of the synaptic vesicle protein Rabphilin-3A in neurotransmitter release at the squid giant synapse. Presynaptic microinjection of recombinant Rabphilin-3A reversibly inhibited the exocytotic release of neurotransmitter. Injection of fragments of Rabphilin-3A indicate that at least two distinct regions of the protein inhibit neurotransmitter release: the NH2-terminal region that binds Rab3A and is phosphorylated by protein kinases and the two C2 domains that interact with calcium, phospholipid, and β-adducin. Each of the inhibitory fragments and the full-length protein had separate effects on presynaptic morphology, suggesting that individual domains were inhibiting a subset of the reactions in which the full-length protein participates. In addition to inhibiting exocytosis, constructs containing the NH2 terminus of Rabphilin-3A also perturbed the endocytotic pathway, as indicated by changes in the membrane areas of endosomes, coated vesicles, and the plasma membrane. These results indicate that Rabphilin-3A regulates synaptic vesicle traffic and appears to do so at distinct stages of both the exocytotic and endocytotic pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rabphilin-3A: A Multifunctional Regulator of Synaptic Vesicle Traffic

Burns

Sasaki

Takai

et al. 1998

The Journal of General Physiology

Self Cite

103

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“…A point mutation in this region of Sly1p renders the protein capable of restoring SNARE complex assembly and secretion in the absence of Ypt1p (Dascher et al, 1991;L upashin and Waters, 1997), suggesting that the mutated Sly1p has a conformation required for proper vesicle traffic that the wild-type Sly1p adopts only after induction by Ypt1p (Dascher et al, 1991). Because secpep3 inhibits the s-Sec1/ s-syntaxin interaction, one may infer that this domain of s-Sec1 could be both subject to regulation by GTPases, such as the squid neuronal Rab3A (Chin and Goldman, 1992;Burns et al, 1995), and involved in syntaxin binding, thus providing a site for crosstalk between the three proteins. Further dissection of Sec1 protein f unctions, in particular identification of the molecular interactions that specif y the negative and positive roles of these proteins, will be required to elucidate the precise roles that Sec1 proteins play in both constitutive and regulated membrane fusion.…”

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confidence: 99%

A Neuronal Sec1 Homolog Regulates Neurotransmitter Release at the Squid Giant Synapse

et al. 1998

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Sec1-related proteins are essential for membrane fusion at distinct stages of the constitutive and regulated secretory pathways in eukaryotic cells. Studies of neuronal isoforms of the Sec1 protein family have yielded evidence for both positive and negative regulatory functions of these proteins in neurotransmitter release. Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1 proteins and examined its function in neurotransmitter release at the squid giant synapse. Microinjection of s-Sec1 into the presynaptic terminal of the giant synapse inhibited evoked neurotransmitter release, but this effect was prevented by coinjecting the cytoplasmic domain of squid syntaxin (s-syntaxin), one of the binding partners of s-Sec1. A 24 amino acid peptide fragment of s-Sec1, which inhibited the binding of s-Sec1 to s-syntaxin in vitro, completely blocked release, suggesting an essential function of the s-Sec1/s-syntaxin interaction in transmitter release. Electron microscopy showed that injection of s-Sec1 did not change the spatial distribution of synaptic vesicles at presynaptic release sites ("active zones"), whereas the inhibitory peptide increased the number of docked vesicles. These distinct morphological effects lead us to conclude that Sec1 proteins function at different stages of synaptic vesicle exocytosis, and that an interaction of s-Sec1 with syntaxin-at a stage blocked by the peptide-is necessary for docked vesicles to fuse.

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et al. 2001

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Degranulation and membrane fusion by neutrophils are essential to host defense. We sought homologues of neuron-specific fusion proteins in human neutrophils and in their precursors, the promyelocytic cell line HL-60. We screened a differentiated HL-60 library and obtained an 848 bp sequence with a 351 bp open reading frame, identical to that published for human VAMP-2 and including 5' and 3' untranslated regions. RNA from HL-60 cells during differentiation into the neutrophil lineage was subjected to Northern blot analysis. which revealed a transcript of approximately 1050 bp at all stages of differentiation. The amount of these transcripts increased approximately threefold during differentiation, a finding confirmed by quantitative RT-PCR. We also detected mRNA for VAMP-2 in human neutrophils and monocytes using RT-PCR. In like fashion, transcripts of syntaxin-4, another fusion protein, were recovered from a neutrophil cDNA library. As with VAMP-2, expression of syntaxin-4 (determined by Northern blots) also increased, but by only 50%, during differentiation of HL-60 cells. These studies demonstrate that neutrophils and their progenitors possess mRNA for the fusion proteins VAMP-2 and syntaxin-4, and that their transcription increases during differentiation, concurrent with the functional maturation of myeloid cells.

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Proteins Involved in Synaptic Vesicle Docking and Fusion

Cited by 4 publications

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Rabphilin-3A: A Multifunctional Regulator of Synaptic Vesicle Traffic

Rabphilin-3A: A Multifunctional Regulator of Synaptic Vesicle Traffic

A Neuronal Sec1 Homolog Regulates Neurotransmitter Release at the Squid Giant Synapse

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