PMID- 10383386
OWN - NLM
STAT- MEDLINE
DCOM- 19990727
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 27
DP  - 1999 Jul 2
TI  - Synaptogyrins regulate Ca2+-dependent exocytosis in PC12 cells.
PG  - 18893-901
AB  - Synaptogyrins constitute a family of synaptic vesicle proteins of unknown
      function. With the full-length structure of a new brain synaptogyrin isoform, we 
      now show that the synaptogyrin family in vertebrates includes two neuronal and
      one ubiquitous isoform. All of these synaptogyrins are composed of a short
      conserved N-terminal cytoplasmic sequence, four homologous transmembrane regions,
      and a variable cytoplasmic C-terminal tail that is tyrosine-phosphorylated. The
      localization, abundance, and conservation of synaptogyrins suggest a function in 
      exocytosis. To test this, we employed a secretion assay in PC12 cells expressing 
      transfected human growth hormone (hGH) as a reporter protein. When Ca2+-dependent
      hGH secretion from PC12 cells was triggered by high K+ or alpha-latrotoxin,
      co-transfection of all synaptogyrins with hGH inhibited hGH exocytosis as
      strongly as co-transfection of tetanus toxin light chain. Synaptophysin I, which 
      is distantly related to synaptogyrins, was also inhibitory but less active.
      Inhibition was independent of the amount of hGH expressed but correlated with the
      amount of synaptogyrin transfected. Inhibition of exocytosis was not observed
      with several other synaptic proteins, suggesting specificity. Analysis of the
      regions of synaptogyrin required for inhibition revealed that the conserved
      N-terminal domain of synaptogyrin is essential for inhibition, whereas the long
      C-terminal cytoplasmic tail is largely dispensable. Our results suggest that
      synaptogyrins are conserved components of the exocytotic apparatus, which
      function as regulators of Ca2+-dependent exocytosis.
FAU - Sugita, S
AU  - Sugita S
AD  - Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes
      Medical Institute, The University of Texas Southwestern Medical Center, Dallas,
      Texas 75235-9050, USA.
FAU - Janz, R
AU  - Janz R
FAU - Sudhof, T C
AU  - Sudhof TC
LA  - eng
SI  - GENBANK/AF117207
SI  - GENBANK/AU035405
SI  - GENBANK/AU035767
GR  - R01-MH52804/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Spider Venoms)
RN  - 0 (Synaptogyrins)
RN  - 0 (Synaptophysin)
RN  - 0 (Tetanus Toxin)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 65988-34-3 (alpha-latrotoxin)
RN  - RWP5GA015D (Potassium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Calcium/*metabolism
MH  - Conserved Sequence
MH  - Exocytosis/*drug effects
MH  - Human Growth Hormone/metabolism
MH  - Humans
MH  - Membrane Proteins/chemistry/*pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/chemistry/*pharmacology
MH  - PC12 Cells
MH  - Potassium/metabolism
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Spider Venoms/metabolism
MH  - Synaptogyrins
MH  - Synaptophysin/pharmacology
MH  - Tetanus Toxin/pharmacology
EDAT- 1999/06/26 00:00
MHDA- 1999/06/26 00:01
CRDT- 1999/06/26 00:00
PHST- 1999/06/26 00:00 [pubmed]
PHST- 1999/06/26 00:01 [medline]
PHST- 1999/06/26 00:00 [entrez]
AID - 10.1074/jbc.274.27.18893 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 2;274(27):18893-901. doi: 10.1074/jbc.274.27.18893.