Cytoplasmic architecture of the axon terminal: Filamentous strands specifically associated with synaptic vesicles

Gotow, Takahiro; Miyaguchi, Katsuyuki; Hashimoto, Paulo H.

doi:10.1016/0306-4522(91)90143-c

Cited by 90 publications

(61 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Slowly releasing granules undergo greater lateral translocation before the fusion event than do rapidly releasing or nonfusing secretory granules during cholinergic stimulation in chromaffin cells (28). These results, together with the existence of a subplasmalemmal actin network in presynaptic terminals, imply that SVs in the subplasmalemmal region might be mobile in the nano-scale range (29).…”

Section: Discussionmentioning

confidence: 88%

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Lee

2012

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that contribute little to synchronous release during action potentials but are release competent when stimulated by sucrose or by direct intracellular application of calcium. It has been noted that the proximity of a release-competent SV to the calcium source is one of the primary factors that differentiate reluctant SVs from fastreleasing ones at the calyx of Held synapse. It has not been known whether reluctant SVs can be converted into fast-releasing ones. Here we show that reluctant SVs are recruited rapidly in an actindependent manner to become fast-releasing SVs once the pool of fast-releasing SVs is depleted by a short depolarization. Recovery of the pool of fast-releasing SVs was accompanied by a parallel reduction in the number of reluctant SVs. Quantitative analysis of the time course of depletion of fast-releasing SVs during high-frequency stimulation revealed that in the early phase of stimulation reluctant SVs are converted rapidly into fast-releasing ones, thereby counteracting short-term depression. During the late phase, however, after reluctant vesicles have been used up, another process of calmodulindependent recruitment of fast-releasing SVs is activated. These results document that reluctant SVs have a role in short-term plasticity and support the hypothesis of positional priming, which posits that reluctant vesicles are converted into fast-releasing ones via relocation closer to Ca 2+ -channels.readily releasable pool | synaptic vesicle dynamics S ynaptic strength is determined by quantal size, the number of release-competent synaptic vesicles (SVs), and their release probability (Pr). The estimate for the number of release-competent SVs, which also is referred to as the "readily releasable pool (RRP) size," depends heavily on the method used for its determination. The RRP size estimated by a cumulative plot of the excitatory postsynaptic currents (EPSC) amplitudes evoked by high-frequency afferent fiber stimulation (RRP cum ) is smaller than that estimated by the application of a hypertonic sucrose solution or presynaptic strong depolarization (1-3). This discrepancy reflects the presence of reluctant SVs, which are scarcely released by an action potential (AP) at glutamatergic synaptic terminals. Consistently, deconvolution analysis of EPSCs evoked by a long depolarizing pulse at the calyx of Held revealed that release-competent SVs can be separated into fast-and slowreleasing SV pools (FRP and SRP, respectively) (4). The FRP vesicles are responsible for phasic release during a high-frequency train of action potentials (APs), whereas the SRP vesicles contribute primarily to asynchronous release, when the intracellular concentration of calcium ions ([Ca 2+ ]) is increased globally during the late period of the train (2). Thus, SRP vesicles can be regarded largely as reluctant SVs at the calyx of Held.Despite the evidence for the presence of reluctant SVs at glutamatergic synapses, their role in short-term plasticity i...

show abstract

Section: Discussionmentioning

confidence: 88%

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Lee

2012

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

show abstract

“…In neurons, the plasma membrane of the presynaptic compartment contains the so-called active zone, a specialized region where synaptic vesicles dock and fuse (2,3). The active zone is characterized ultrastructurally as an electron-dense region of cytoskeletal filaments under the plasma membrane where synaptic vesicles are clustered (4,5). It is thought that the cytoskeletal matrix associated with the active zone (CAZ) 1 plays a fundamental role in regulating the mobilization of synaptic vesicles and defining release sites (6).…”

mentioning

confidence: 99%

Piccolo, a Ca2+ Sensor in Pancreatic β-Cells

Fujimoto

Shibasaki

Yokoi

et al. 2002

Journal of Biological Chemistry

184

View full text Add to dashboard Cite

We have previously shown that cAMP-binding protein cAMP-guanidine nucleotide exchange factor II (GEFII) (or Epac2) interacting with Rim2 is involved in cAMPdependent, protein kinase A-independent exocytosis in pancreatic ␤-cells. The action of the cAMP-GEFII⅐Rim2 complex requires both intracellular cAMP and Ca 2؉ . Although Rim2 has C 2 domains, its role as a Ca 2؉ sensor has remained unclear. In the present investigation, we have discovered that Piccolo, a CAZ (cytoskeletal matrix associated with the active zone) protein in neurons that is structurally related to Rim2, also binds to cAMP-GE-FII and that it forms both homodimer and heterodimer with Rim2 in a Ca 2؉ -dependent manner, whereas Rim2 alone does not form the homodimer. The association of Piccolo⅐Rim2 heterodimerization is stronger than Piccolo⅐Piccolo homodimerization. Treatment of pancreatic islets with antisense oligodeoxynucleotides against Piccolo inhibits insulin secretion induced by cAMP analog 8-bromo-cyclic AMP plus high glucose stimulation. These results suggest that Piccolo serves as a Ca 2؉ sensor in exocytosis in pancreatic ␤-cells and that the formation of a cAMP-GEFII⅐Rim2⅐Piccolo complex is important in cAMP-induced insulin secretion. In addition, this study suggests that CAZ proteins similar to those in neurons are also function in pancreatic ␤-cells.

show abstract

“…This is consistent with the particles being synapsin 1 head domains. The diameter of the synapsin 1 head has been put at 15 2 nm in metal-shadowed preparations (Steiner et al, 1987;Landis et al, 1988;Hirokawa et al, 1989;Gotow et al, 1991). Synapsin 1 tails are not detected in our negatively stained preparations, probably because they are too thin.…”

Section: Bundling Of Microtubules By Synapsinmentioning

confidence: 85%

“…A 'releasable pool' can undergo exocytosis as soon as a nerve terminal is depolarised; vesicles are recruited into this pool from a 'reserve pool' for exocytosis at a subsequent round of release. Electron microscopy of nerve terminals in situ reveals that small synaptic vesicles (SSV), which store the neurotransmitter glutamate (Burger et al, 1989), are organised in two distinct ways, which probably correspond to the two pools (Landis et al, 1988;Heuser, 1989;Hirokawa et al, 1989;Gotow et al, 1991). The releasable pool consists of SSV docked at the active zone, a region of the presynaptic plasma membrane which is active in exocytosis.…”

mentioning

confidence: 99%

Bundling of microtubules by synapsin 1

Bennett

Baines

1992

European Journal of Biochemistry

View full text Add to dashboard Cite

Synapsin 1 is a nerve terminal phosphoprotein whose role seems to encompass the linking of small synaptic vesicles to the cytoskeleton. Synapsin 1 can join small synaptic vesicles to neuronal spectrin, microfilaments and microtubules; it can also bundle microtubules and microfilaments. In this paper, the mode of interaction between synapsin 1 and microtubules has been investigated. Bundling is shown to be highly cooperative: the apparent Hill coefficient is 3.06 ± 0.3, and bundling is half‐maximal at 0.63 ± 0.02 μM. Bundling occurs either when whole synapsin 1 preparations (containing monomers and oligomers) or when monomeric synapsin 1 is added to microtubules. However, it is not clear that synapsin 1 remains monomeric in the presence of microtubules. Synapsin 1‐microtubule mixtures contain two types of filament. One type is characterised by microtubules often with synapsin 1 bound to their surface. The other type is composed of filaments of diameter 15 ± 5 nm. This filament type is granular and made up in part of 14‐nm‐diameter particles. These dimensions are consistent with their being made up of polymerised synapsin 1. It is possible that microtubules induce the polymerisation of synapsin 1. Synapsin 1 had independent tubulin binding sites in the N‐terminal head domain and in the C‐terminal tail domain. Whole synapsin 1 can interact with tubulin after it has been digested to remove the tubulin C terminus (des‐C‐terminal tubulin). The interaction of des‐C‐terminal tubulin with synapsin 1 appears to be via the head domain, since 125I‐des‐C‐terminal tubulin only shows specific binding to the head domain on gel blots. By contrast intact tubulin binds to both head and tail domains. Binding to the tail domain can be inhibited by a synthetic peptide representing the microtubule‐associated protein 2 (MAP2) binding site of class II β tubulin. These results suggest a model for microtubule bundling by synapsin 1 in which independent sites in the head and tail domains of synapsin 1 cross‐link microtubules by interactions with two distinct sites in tubulin.

show abstract

Cytoplasmic architecture of the axon terminal: Filamentous strands specifically associated with synaptic vesicles

Cited by 90 publications

References 36 publications

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool

Piccolo, a Ca2+ Sensor in Pancreatic β-Cells

Bundling of microtubules by synapsin 1

Contact Info

Product

Resources

About