PMID- 10358015
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 24
DP  - 1999 Jun 11
TI  - Homo- and heterodimerization of synapsins.
PG  - 16747-53
AB  - In vertebrates, synapsins constitute a family of synaptic vesicle proteins
      encoded by three genes. Synapsins contain a central ATP-binding domain, the
      C-domain, that is highly homologous between synapsins and evolutionarily
      conserved in invertebrates. The crystal structure of the C-domain from synapsin I
      revealed that it constitutes a large (>300 amino acids), independently folded
      domain that forms a tight dimer with or without bound ATP. We now show that the
      C-domains of all synapsins form homodimers, and that in addition, C-domains from 
      different synapsins associate into heterodimers. This conclusion is based on four
      findings: 1) in yeast two-hybrid screens with full-length synapsin IIa as a bait,
      the most frequently isolated prey cDNAs encoded the C-domain of synapsins; 2)
      quantitative yeast two-hybrid protein-protein binding assays demonstrated
      pairwise strong interactions between all synapsins; 3) immunoprecipitations from 
      transfected COS cells confirmed that synapsin II heteromultimerizes with
      synapsins I and III in intact cells, and similar results were obtained with
      bacterial expression systems; and 4) quantification of the synapsin III level in 
      synapsin I/II double knockout mice showed that the level of synapsin III is
      decreased by 50%, indicating that heteromultimerization of synapsin III with
      synapsins I or II occurs in vivo and is required for protein stabilization. These
      data suggest that synapsins coat the surface of synaptic vesicles as homo- and
      heterodimers in which the C-domains of the various subunits have distinct
      regulatory properties and are flanked by variable C-terminal sequences. The data 
      also imply that synapsin III does not compensate for the loss of synapsins I and 
      II in the double knockout mice.
FAU - Hosaka, M
AU  - Hosaka M
AD  - Center for Basic Neuroscience and Department of Molecular Genetics, Howard Hughes
      Medical Institute, The University of Texas Southwestern Medical School, Dallas,
      Texas 75235, USA.
FAU - Sudhof, T C
AU  - Sudhof TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Synapsins)
SB  - IM
MH  - Animals
MH  - Antibody Specificity
MH  - Brain Chemistry
MH  - Cloning, Molecular
MH  - Dimerization
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Binding
MH  - Protein Isoforms/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Saccharomyces cerevisiae/genetics
MH  - Synapsins/genetics/immunology/*metabolism
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1074/jbc.274.24.16747 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 11;274(24):16747-53. doi: 10.1074/jbc.274.24.16747.