PMID- 29194628
OWN - NLM
STAT- MEDLINE
DCOM- 20190621
LR  - 20190621
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 596
IP  - 8
DP  - 2018 Apr 15
TI  - The presynaptic scaffolding protein Piccolo organizes the readily releasable pool 
      at the calyx of Held.
PG  - 1485-1499
LID - 10.1113/JP274885 [doi]
AB  - KEY POINTS: Bassoon and Piccolo do not mediate basal synaptic vesicle release at 
      a high-frequency synapse. Knockdown of Bassoon increases short-term depression at 
      the calyx of Held. Both Bassoon and Piccolo have shared functions in synaptic 
      vesicle replenishment during high-frequency synaptic transmission. Piccolo 
      organizes the readily releasable pool of synaptic vesicles. It safeguards a 
      fraction of them to be not immediately available for action potential-induced 
      release. This enables the synapse to sustain high-frequency synaptic transmission 
      over long periods. ABSTRACT: Synaptic vesicles (SVs) are released at the active 
      zone (AZ), a specialized region of the presynaptic plasma membrane organized by a 
      highly interconnected network of multidomain proteins called the cytomatrix of 
      the active zone (CAZ). Two core components of the CAZ are the large, highly 
      homologous scaffolding proteins Bassoon and Piccolo, whose function is not well 
      understood. To investigate their role in synaptic transmission, we established 
      the small hairpin RNA (shRNA)-mediated in vivo knockdown (KD) of Bassoon and 
      Piccolo at the rat calyx of Held synapse. KD of Bassoon and Piccolo, separately 
      or simultaneously, did not affect basic SV release. However, short-term 
      depression (STD) was prominently increased by the KD of Bassoon, whereas KD of 
      Piccolo only had a minor effect. The observed alterations in STD were readily 
      explained by reduced SV replenishment in synapses deficient in either of the 
      proteins. Thus, the regulation of SV refilling during ongoing synaptic activity 
      is a shared function of Bassoon and Piccolo, although Bassoon appears to be more 
      efficient. Moreover, we observed the recruitment of slowly-releasing SVs of the 
      readily-releasable pool (RRP), which are normally not available for action 
      potential-induced release, during high-frequency stimulation in Piccolo-deficient 
      calyces. Therefore, the results obtained in the present study suggest a novel and 
      specific role for Piccolo in the organization of the subpools of the RRP.
CI  - (c) 2017 The Authors. The Journal of Physiology (c) 2017 The Physiological Society.
FAU - Parthier, Daniel
AU  - Parthier D
AUID- ORCID: 0000-0001-8775-024X
AD  - Institute of Anatomy and Cell Biology, Department of Functional Neuroanatomy, 
      Heidelberg University, Heidelberg, Germany.
AD  - Present address: Neuroscience Research Center, Charite Universitatsmedizin, 
      Berlin, Germany.
FAU - Kuner, Thomas
AU  - Kuner T
AD  - Institute of Anatomy and Cell Biology, Department of Functional Neuroanatomy, 
      Heidelberg University, Heidelberg, Germany.
FAU - Korber, Christoph
AU  - Korber C
AUID- ORCID: 0000-0003-1418-9724
AD  - Institute of Anatomy and Cell Biology, Department of Functional Neuroanatomy, 
      Heidelberg University, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180104
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Bsn protein, rat)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Pclo protein, rat)
SB  - IM
CIN - J Physiol. 2018 Apr 15;596(8):1315-1316. PMID: 29446080
MH  - Animals
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - Female
MH  - Male
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neuropeptides/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synapses/*metabolism/physiology
MH  - *Synaptic Potentials
MH  - Synaptic Vesicles/*metabolism
MH  - Trapezoid Body/cytology/metabolism
PMC - PMC5899986
OTO - NOTNLM
OT  - active zone
OT  - replenishment
OT  - synaptic vesicles
EDAT- 2017/12/02 06:00
MHDA- 2019/06/22 06:00
PMCR- 2019/04/15
CRDT- 2017/12/02 06:00
PHST- 2017/07/06 00:00 [received]
PHST- 2017/11/28 00:00 [accepted]
PHST- 2017/12/02 06:00 [pubmed]
PHST- 2019/06/22 06:00 [medline]
PHST- 2017/12/02 06:00 [entrez]
PHST- 2019/04/15 00:00 [pmc-release]
AID - TJP12749 [pii]
AID - 10.1113/JP274885 [doi]
PST - ppublish
SO  - J Physiol. 2018 Apr 15;596(8):1485-1499. doi: 10.1113/JP274885. Epub 2018 Jan 4.