PMID- 10373452
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to
      dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?
PG  - 18446-54
AB  - In yeast two-hybrid screens for proteins that bind to SNAP-25 and may be involved
      in exocytosis, we isolated a protein called EHSH1 (for EH domain/SH3
      domain-containing protein). Cloning of full-length cDNAs revealed that EHSH1 is
      composed of an N-terminal region with two EH domains, a central region that is
      enriched in lysine, leucine, glutamate, arginine, and glutamine (KLERQ domain),
      and a C-terminal region comprised of five SH3 domains. The third SH3 domain is
      alternatively spliced. Data bank searches demonstrated that EHSH1 is very similar
      to Xenopus and human intersectins and to human SH3P17. In addition, we identified
      expressed sequence tags that encode a second isoform of EHSH1, called EHSH2.
      EHSH1 is abundantly expressed in brain and at lower levels in all other tissues
      tested. In binding studies, we found that the central KLERQ domain of EHSH1 binds
      to recombinant or native brain SNAP-25 and SNAP-23. The C-terminal SH3 domains,
      by contrast, quantitatively interact with dynamin, a protein involved in
      endocytosis. Dynamin strongly binds to the alternatively spliced central SH3
      domain (SH3C) and the two C-terminal SH3 domains (SH3D and SH3E) but not to the
      N-terminal SH3 domains (SH3A and SH3B). Immunoprecipitations confirmed that both 
      dynamin and SNAP-25 are complexed to EHSH1 in brain. Our data suggest that
      EHSH1/intersectin may be a novel adaptor protein that couples endocytic membrane 
      traffic to exocytosis. The ability of multiple SH3 domains in EHSH1 to bind to
      dynamin suggests that EHSH1 can cluster several dynamin molecules in a manner
      that is regulated by alternative splicing.
FAU - Okamoto, M
AU  - Okamoto M
AD  - Center for Basic Neuroscience, Howard Hughes Medical Institute, and the
      Department of Molecular Genetics, The University of Texas Southwestern Medical
      School, Dallas Texas 75235, USA.
FAU - Schoch, S
AU  - Schoch S
FAU - Sudhof, T C
AU  - Sudhof TC
LA  - eng
SI  - GENBANK/AF127798
SI  - GENBANK/AF132672
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 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Carrier Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SNAP25 protein, human)
RN  - 0 (Snap25 protein, Drosophila)
RN  - 0 (Snap25 protein, mouse)
RN  - 0 (Snap25 protein, rat)
RN  - 0 (Synaptosomal-Associated Protein 25)
RN  - 0 (intersectin 1)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Drosophila
MH  - Drosophila Proteins
MH  - Dynamins
MH  - Endocytosis
MH  - Exocytosis
MH  - GTP Phosphohydrolases/*metabolism
MH  - Gene Library
MH  - Humans
MH  - *Membrane Proteins
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*metabolism
MH  - Protein Binding
MH  - Rats
MH  - Synaptosomal-Associated Protein 25
MH  - Xenopus
MH  - *src Homology Domains
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18446 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18446-54. doi: 10.1074/jbc.274.26.18446.