PMID- 10531343
OWN - NLM
STAT- MEDLINE
DCOM- 19991216
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 44
DP  - 1999 Oct 29
TI  - Conserved N-terminal cysteine motif is essential for homo- and heterodimer
      formation of synaptotagmins III, V, VI, and X.
PG  - 31421-7
AB  - The synaptotagmins now constitute a large family of membrane proteins
      characterized by one transmembrane region and two C2 domains. Dimerization of
      synaptotagmin (Syt) I, a putative low affinity Ca(2+) sensor for neurotransmitter
      release, is thought to be important for expression of function during exocytosis 
      of synaptic vesicles. However, little is known about the self-dimerization
      properties of other isoforms. In this study, we demonstrate that a subclass of
      synaptotagmins (III, V, VI, and X) (Ibata, K., Fukuda, M., and Mikoshiba, K.
      (1998) J. Biol. Chem. 273, 12267-12273) forms beta-mercaptoethanol-sensitive
      homodimers and identify three evolutionarily conserved cysteine residues at the N
      terminus (N-terminal cysteine motif, at amino acids 10, 21, and 33 of mouse Syt
      III) that are not conserved in other isoforms. Site-directed mutagenesis of these
      cysteine residues and co-immunoprecipitation experiments clearly indicate that
      the first cysteine residue is essential for the stable homodimer formation of Syt
      III, V, or VI, and heterodimer formation between Syts III, V, VI, and X. We also 
      show that native Syt III from mouse brain forms a beta-mercaptoethanol-sensitive 
      homodimer. Our results suggest that the cysteine-based heterodimerization between
      Syt III and Syt V, VI, or X, which have different biochemical properties, may
      modulate the proposed function of Syt III as a putative high affinity Ca(2+)
      sensor for neurotransmitter release.
FAU - Fukuda, M
AU  - Fukuda M
AD  - Developmental Neurobiology Laboratory, Brain Science Institute, Institute of
      Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198,
      Japan.
FAU - Kanno, E
AU  - Kanno E
FAU - Mikoshiba, K
AU  - Mikoshiba K
LA  - eng
SI  - GENBANK/AB026802
SI  - GENBANK/AB026803
SI  - GENBANK/AB026804
SI  - GENBANK/AB026805
SI  - GENBANK/AB026806
SI  - GENBANK/AB026807
SI  - GENBANK/AB026808
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 (Calcium-Binding Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Syt5 protein, mouse)
RN  - 0 (Syt9 protein, mouse)
RN  - 134193-27-4 (Synaptotagmins)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Calcium-Binding Proteins
MH  - Conserved Sequence
MH  - *Cysteine/genetics
MH  - Dimerization
MH  - Membrane Glycoproteins/*chemistry/classification/genetics/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nerve Tissue Proteins/*chemistry/classification/genetics/*metabolism
MH  - Phylogeny
MH  - Protein Binding
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Synaptotagmins
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1074/jbc.274.44.31421 [doi]
AID - S0021-9258(19)51637-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 29;274(44):31421-7. doi: 10.1074/jbc.274.44.31421.