scholarly journals Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles

2007 ◽  
Vol 179 (7) ◽  
pp. 1481-1496 ◽  
Author(s):  
Tomoko Ohyama ◽  
Patrik Verstreken ◽  
Cindy V. Ly ◽  
Tanja Rosenmund ◽  
Akhila Rajan ◽  
...  

Posttranslational modification through palmitoylation regulates protein localization and function. In this study, we identify a role for the Drosophila melanogaster palmitoyl transferase Huntingtin-interacting protein 14 (HIP14) in neurotransmitter release. hip14 mutants show exocytic defects at low frequency stimulation and a nearly complete loss of synaptic transmission at higher temperature. Interestingly, two exocytic components known to be palmitoylated, cysteine string protein (CSP) and SNAP25, are severely mislocalized at hip14 mutant synapses. Complementary DNA rescue and localization experiments indicate that HIP14 is required solely in the nervous system and is essential for presynaptic function. Biochemical studies indicate that HIP14 palmitoylates CSP and that CSP is not palmitoylated in hip14 mutants. Furthermore, the hip14 exocytic defects can be suppressed by targeting CSP to synaptic vesicles using a chimeric protein approach. Our data indicate that HIP14 controls neurotransmitter release by regulating the trafficking of CSP to synapses.

2017 ◽  
Author(s):  
Frédéric Doussau ◽  
Hartmut Schmidt ◽  
Kevin Dorgans ◽  
Antoine M. Valera ◽  
Bernard Poulain ◽  
...  

ABSTRACTThe segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are differentially poised for exocytosis shapes short-term plasticity at depressing synapses. Here, we used in vitro recording and modeling of synaptic activity at the facilitating mice cerebellar granule cell to Purkinje cell synapse to demonstrate the existence of two sub-pools of vesicles in the RRP that can be differentially recruited upon fast changes in the stimulation frequency. We show that upon low-frequency stimulation, a population of fully-releasable vesicles is silenced, leading to full blockage of synaptic transmission. A second population of vesicles, reluctant to release by simple stimuli, is recruited in a millisecond time scale by high-frequency stimulation to support an ultrafast recovery of neurotransmitter release after low-frequency depression. The frequency-dependent mobilization or silencing of sub-pools of vesicles in granule cell terminals should play a major role in the filtering of sensorimotor information in the cerebellum.


2005 ◽  
Vol 50 (12) ◽  
pp. 1005-1013 ◽  
Author(s):  
Konosuke Yamasaki ◽  
Shuitsu Harada ◽  
Itsuro Higuchi ◽  
Mitsuhiro Osame ◽  
Gakuji Ito

1957 ◽  
Vol 40 (3) ◽  
pp. 435-450 ◽  
Author(s):  
David P. C. Lloyd

An assemblage of individual motoneurons constituting a synthetic motoneuron pool has been studied from the standpoint of relating monosynaptic reflex responses to frequency of afferent stimulation. Intensity of low frequency depression is not a simple function of transmitter potentiality. As frequency of stimulation increases from 3 per minute to 10 per second, low frequency depression increases in magnitude. Between 10 and approximately 60 per second low frequency depression apparently diminishes and subnormality becomes a factor in causing depression. At frequencies above 60 per second temporal summation occurs, but subnormality limits the degree of response attainable by summation. At low stimulation frequencies rhythm is determined by stimulation frequency. Interruptions of rhythmic firing depend solely upon temporal fluctuation of excitability. At high frequency of stimulation rhythm is determined by subnormality rather than inherent rhythmicity, and excitability fluctuation leads to instability of response rhythm. In short, whatever the stimulation frequency, random excitability fluctuation is the factor disrupting rhythmic response. Monosynaptic reflex response latency is stable during high frequency stimulation as it is in low frequency stimulation provided a significant extrinsic source of random bombardment is not present. In the presence of powerful random bombardment discharge may become random with respect to monosynaptic afferent excitation provided the latter is feeble. When this occurs it does so equally at low frequency and high frequency. Thus temporal summation is not a necessary factor. There is, then, no remaining evidence to suggest that the agency for temporal summation in the monosynaptic system becomes a transmitting agency in its own right.


1993 ◽  
Vol 69 (3) ◽  
pp. 953-964 ◽  
Author(s):  
P. W. Glimcher ◽  
D. L. Sparks

1. The first experiment of this study determined the effects of low-frequency stimulation of the monkey superior colliculus on spontaneous saccades in the dark. Stimulation trains, subthreshold for eliciting short-latency fixed-vector saccades, were highly effective at biasing the metrics (direction and amplitude) of spontaneous movements. During low-frequency stimulation, the distribution of saccade metrics was biased toward the direction and amplitude of movements induced by suprathreshold stimulation of the same collicular location. 2. Low-frequency stimulation biased the distribution of saccade metrics but did not initiate movements. The distribution of intervals between stimulation onset and the onset of the next saccade did not differ significantly from the distribution of intervals between an arbitrary point in time and the onset of the next saccade under unstimulated conditions. 3. Results of our second experiment indicate that low-frequency stimulation also influenced the metrics of visually guided saccades. The magnitude of the stimulation-induced bias increased as stimulation current or frequency was increased. 4. The time course of these effects was analyzed by terminating stimulation immediately before, during, or after visually guided saccades. Stimulation trains terminated at the onset of a movement were as effective as stimulation trains that continued throughout the movement. No effects were observed if stimulation ended 40–60 ms before the movement began. 5. These results show that low-frequency collicular stimulation can influence the direction and amplitude of spontaneous or visually guided saccades without initiating a movement. These data are compatible with the hypothesis that the collicular activity responsible for specifying the horizontal and vertical amplitude of a saccade differs from the type of collicular activity that initiates a saccade.


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