The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1.

Hirokawa, Nobutaka; Sobue, Kenji; Kanda, Keiko; Harada, Akira; Yorifuji, Hiroshi

doi:10.1083/jcb.108.1.111

Cited by 474 publications

(400 citation statements)

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“…Fewer studies have been made regarding the presynaptic role of actin, although actin has been shown to be an important constituent of the presynaptic terminal (Fifkova and Delay, 1982;Hirokawa et al, 1989) and the active zones (Phillips et al, 2001). At synapses, physiological studies have postulated that actin has important roles in vesicle mobilization (Bernstein and Bamberg, 1989;Wang et al, 1996;Kuromi and Kidokoro, 1998).…”

Section: Roles Of Actin In Vesicle Recruitmentmentioning

confidence: 99%

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

2003

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Depletion and replenishment of pools of synaptic vesicles are important determinants of short-term synaptic plasticity, but the underlying molecular mechanisms are not yet clear. As a first step toward understanding the process of vesicle recruitment, we have applied various specific agents directly to the presynaptic terminal of the calyx of Held synapse. Here we show that the nonhydrolyzable ATP analog ATP-␥S retards the recovery from vesicle pool depletion, as does latrunculin A. Phalloidin has no effects on recovery, suggesting that dynamic actin reorganization is not necessary. Unexpectedly, neither N-ethylmaleimide nor staurosporine affected the recovery, calling into question the role of N-ethylmaleimide-sensitive factor and protein kinases. The results suggest that intact actin polymerization is involved in vesicle recruitment.

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Section: Roles Of Actin In Vesicle Recruitmentmentioning

confidence: 99%

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

2003

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“…Previous studies have shown that presynaptic F-actin cytoskeleton plays an important role in the formation and maintenance of SV clusters (Hirokawa et al, 1989;Dai and Peng, 1996a;Peng et al, 1997;Richards et al, 2004). F-actin assembly is a major cellular process that consumes metabolic energy in neurons (Bernstein and Bamburg, 2003).…”

Section: Regulation Of F-actin Assembly By Mitochondrial ⌬⌿ Mmentioning

confidence: 99%

“…RRP is a population of vesicles docked at the active zone and primed for release, whereas RP is a cluster of vesicles residing distally from the active zone. Structural studies with electron microscopy and immunolabeling have shown that F-actin is associated with SV clusters within the nerve terminal (Hirokawa et al, 1989;Dai and Peng, 1996a;Bloom et al, 2003). At Drosophila NMJs, F-actin disruption by cytochalasin D disrupts RP while leaving the RRP intact (Kuromi and Kidokoro, 1998).…”

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confidence: 99%

The Function of Mitochondria in Presynaptic Development at the Neuromuscular Junction

Lee

Peng

2008

MBoC

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Mitochondria with high membrane potential (⌬⌿ m ) are enriched in the presynaptic nerve terminal at vertebrate neuromuscular junctions, but the exact function of these localized synaptic mitochondria remains unclear. Here, we investigated the correlation between mitochondrial ⌬⌿ m and the development of synaptic specializations. Using mitochondrial ⌬⌿ m -sensitive probe JC-1, we found that ⌬⌿ m in Xenopus spinal neurons could be reversibly elevated by creatine and suppressed by FCCP. Along naïve neurites, preexisting synaptic vesicle (SV) clusters were positively correlated with mitochondrial ⌬⌿ m , suggesting a potential regulatory role of mitochondrial activity in synaptogenesis. Indicating a specific role of mitochondrial activity in presynaptic development, mitochondrial ATP synthase inhibitor oligomycin, but not mitochondrial Na ؉ /Ca 2؉ exchanger inhibitor CGP-37157, inhibited the clustering of SVs induced by growth factor-coated beads. Local F-actin assembly induced along spinal neurites by beads was suppressed by FCCP or oligomycin. Our results suggest that a key role of presynaptic mitochondria is to provide ATP for the assembly of actin cytoskeleton involved in the assembly of the presynaptic specialization including the clustering of SVs and mitochondria themselves. INTRODUCTIONMitochondria play multiple roles in cellular functions including cellular metabolism, calcium homeostasis, and programmed cell death. At both peripheral and central synapses, mitochondria are concentrated within the presynaptic nerve terminal as demonstrated by electron microscopic studies and they are presumably related to the transmitter release machinery (Herrera et al., 1985;Robitaille and Tremblay, 1987;Peters et al., 1991). Our previous study found that local synaptogenic signals induce the clustering of not only synaptic vesicles (SVs; Dai and Peng, 1995), but also mitochondria (Lee and Peng, 2006), thus suggesting that the clustering of this organelle is an integral part of presynaptic differentiation. The function of mitochondria at mature neuromuscular junctions (NMJs) has recently been explored. For example, the transmitter release under intense stimulation fails in a Drosophila NMJ mutant lacking presynaptic mitochondria (Guo et al., 2005;Verstreken et al., 2005). The calcium release from mitochondria has been shown to modulate synaptic potentiation at the vertebrate NMJ (Yang et al., 2003). However, the function of presynaptic mitochondria in the development of the NMJ is not yet known.Within the axon, mitochondria undergo bidirectional movement and accumulate at sites of high metabolic activity (Hollenbeck, 1996). The direction of mitochondrial transport is correlated with axonal outgrowth (Morris and Hollenbeck, 1993) and its activity (Miller and Sheetz, 2004), reflected by the electrical potential (⌬⌿ m ) across the inner membrane produced by oxidative phosphorylation-mediated electrochemical equilibrium of H ϩ ions. Previously, we found that mitochondria with high ⌬⌿ m are predominantly localized at the presyna...

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“…The synaptic vesicle protein responsible for this specific attachment is not known. Freezeetch electron microscopy of presynaptic terminals reveals synapsin-like filamentous proteins attached between synaptic vesicles and the cytoskeleton (Landis et al, 1988;Hirokawa et al, 1989).…”

Section: Calcium-calmodulin-dependent Protein Kinase and The Regulatimentioning

confidence: 99%

The glutamatergic nerve terminal

Nicholls

1993

European Journal of Biochemistry

208

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Glutamate as a neurotransmitterThe human brain has about lolo neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these l O I 3 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982;Cotman et al., 1988;Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986;Choi, 1988 ;Meldrum and Garthwaite, 1990).A synapse has a pre-synaptic element responsible for the storage and release of transmitter and a post-synaptic element containing one or more classes of receptor for the transmitter. The potent combination of electrophysiology and molecular cloning has allowed a dramatic advance in our understanding of post-synaptic events. Three classes of post-synaptic ionotropic (possessing an integral ion channel) glutamate receptors have been identified and cloned: the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionatekainate (AMPA/ KA) receptor Nakanishi et al., 1990;Sakmann, 1992), the high-affinity KA receptor (Egebjerg et al., 1991) and the N-methyl D-aSpartate (NMDA) receptor (Moriyoshi et al., 1991 ; Kumar et al., 1991 ;Barnard, 1992). Each can exist in many isoforms by combining subunits formed from distinct genes, by alternative splicing or by post-transcriptional modification (Monyer et al., 1991 ;Burnashev et al., 1992).The AMPNKA receptor is responsible for fast information transfer while the NMDA receptor is only operative when the post-synaptic membrane is independently depolarized by another receptor. This 'associative' behaviour of the latter is believed to underlie aspects of the learning process.

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The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1.

Cited by 474 publications

References 47 publications

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

The Function of Mitochondria in Presynaptic Development at the Neuromuscular Junction

The glutamatergic nerve terminal

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