PMID- 24091420
OWN - NLM
STAT- MEDLINE
DCOM- 20150522
LR  - 20240323
IS  - 1933-6942 (Electronic)
IS  - 1933-6934 (Print)
IS  - 1933-6934 (Linking)
VI  - 7
IP  - 4
DP  - 2013 Oct-Dec
TI  - Mutations in palmitoyl-protein thioesterase 1 alter exocytosis and endocytosis at 
      synapses in Drosophila larvae.
PG  - 267-79
LID - 10.4161/fly.26630 [doi]
AB  - Infantile-onset neuronal ceroid lipofuscinosis (INCL) is a severe pediatric 
      neurodegenerative disorder produced by mutations in the gene encoding 
      palmitoyl-protein thioesterase 1 (Ppt1). This enzyme is responsible for the 
      removal of a palmitate group from its substrate proteins, which may include 
      presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and 
      synaptotagmin. The fruit fly, Drosophila melanogaster, has been a powerful model 
      system for studying the functions of these proteins and the molecular basis of 
      neurological disorders like the NCLs. Genetic modifier screens and tracer uptake 
      studies in Ppt1 mutant larval garland cells have suggested that Ppt1 plays a role 
      in endocytic trafficking. We have extended this analysis to examine the 
      involvement of Ppt1 in synaptic function at the Drosophila larval neuromuscular 
      junction (NMJ). Mutations in Ppt1 genetically interact with temperature sensitive 
      mutations in the Drosophila dynamin gene shibire, accelerating the paralytic 
      behavior of shibire mutants at 27  degrees C. Electrophysiological work in NMJs of 
      Ppt1-deficient larvae has revealed an increase in miniature excitatory junctional 
      potentials (EJPs) and a significant depression of evoked EJPs in response to 
      repetitive (10 hz) stimulation. Endocytosis was further examined in Ppt1-mutant 
      larvae using FM1-43 uptake assays, demonstrating a significant decrease in FM1-43 
      uptake at the mutant NMJs. Finally, Ppt1-deficient and Ppt1 point mutant larvae 
      display defects in locomotion that are consistent with alterations in synaptic 
      function. Taken together, our genetic, cellular, and electrophysiological 
      analyses suggest a direct role for Ppt1 in synaptic vesicle exo- and endocytosis 
      at motor nerve terminals of the Drosophila NMJ.
FAU - Aby, Elizabeth
AU  - Aby E
AD  - Department of Biology; Pomona College; Claremont, CA USA.
FAU - Gumps, Katherine
AU  - Gumps K
AD  - Department of Biology; The College of Charleston; Charleston, SC USA.
FAU - Roth, Amalia
AU  - Roth A
AD  - Department of Biology; Pomona College; Claremont, CA USA.
FAU - Sigmon, Stacey
AU  - Sigmon S
AD  - Department of Biology; The College of Charleston; Charleston, SC USA.
FAU - Jenkins, Sarah E
AU  - Jenkins SE
AD  - Department of Biology; Pomona College; Claremont, CA USA.
FAU - Kim, Joyce J
AU  - Kim JJ
AD  - Department of Biology; Pomona College; Claremont, CA USA.
FAU - Kramer, Nicholas J
AU  - Kramer NJ
AD  - Department of Neuroscience; Pomona College; Claremont, CA USA.
FAU - Parfitt, Karen D
AU  - Parfitt KD
AD  - Department of Biology; Pomona College; Claremont, CA USA; Program in Molecular 
      Biology ; Pomona College; Claremont, CA USA.
FAU - Korey, Christopher A
AU  - Korey CA
AD  - Department of Biology; The College of Charleston; Charleston, SC USA.
LA  - eng
GR  - P20 RR016461/RR/NCRR NIH HHS/United States
GR  - R15 HD052362/HD/NICHD NIH HHS/United States
GR  - P20-RR16461/RR/NCRR NIH HHS/United States
GR  - R15-HD052362/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131003
PL  - United States
TA  - Fly (Austin)
JT  - Fly
JID - 101470897
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (Ppt1 protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Drosophila Proteins/*genetics/metabolism/physiology
MH  - Drosophila melanogaster/cytology/*genetics/physiology
MH  - Endocytosis/*genetics
MH  - Exocytosis/*genetics
MH  - Larva/cytology/genetics/metabolism
MH  - Locomotion/genetics
MH  - Membrane Proteins/*genetics/metabolism/physiology
MH  - Mutation
MH  - Neuromuscular Junction/growth & development/metabolism
MH  - Synapses/metabolism/physiology
MH  - Thiolester Hydrolases
PMC - PMC3896500
OTO - NOTNLM
OT  - Batten disease
OT  - Drosophila
OT  - endocytosis
OT  - exocytosis
OT  - infantile neuronal ceroid lipofuscinosis
OT  - palmitoyl-protein thioesterase-1
OT  - synaptic vesicle cycling
EDAT- 2013/10/05 06:00
MHDA- 2015/05/23 06:00
PMCR- 2014/10/01
CRDT- 2013/10/05 06:00
PHST- 2013/10/05 06:00 [entrez]
PHST- 2013/10/05 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 26630 [pii]
AID - 2013FLY0028R [pii]
AID - 10.4161/fly.26630 [doi]
PST - ppublish
SO  - Fly (Austin). 2013 Oct-Dec;7(4):267-79. doi: 10.4161/fly.26630. Epub 2013 Oct 3.