PMID- 10407024
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 14
DP  - 1999 Jul 15
TI  - Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function 
      in regulating neurotransmitter release.
PG  - 5834-46
AB  - Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate
      vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because
      it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on
      synaptic vesicles, and it dissociates with rab3s from the vesicles during
      exocytosis. Rabphilin contains two C(2) domains, which could function as Ca(2+)
      sensors in exocytosis and is phosphorylated as a function of stimulation.
      However, it is unknown what essential function, if any, rabphilin performs. One
      controversial question regards the respective roles of rab3s and rabphilin in
      localizing each other to synaptic vesicles: although rabphilin is mislocalized in
      rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin 
      for binding of rab3A but not rab3A for binding of rabphilin. To test whether
      rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the
      functions of rabphilin in regulating exocytosis, we have now analyzed knock-out
      mice for rabphilin. Mice that lack rabphilin are viable and fertile without
      obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted
      to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin
      transport to synapses is impaired. These results show that rabphilin binds to
      vesicles via rab3s, consistent with an effector function of rabphilin for a
      synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic
      transmission or plasticity were observed in rabphilin-deficient mice; synaptic
      properties that are impaired in rab3A knock-out mice were unchanged in rabphilin 
      knock-out mice. Our data thus demonstrate that rabphilin is endowed with the
      properties of a rab3 effector but is not essential for the regulatory functions
      of rab3 in synaptic transmission.
FAU - Schluter, O M
AU  - Schluter OM
AD  - Abteilung Molekulare Neurobiologie, Max-Planck-Institut fur Experimentelle
      Medizin, 37075 Goettingen, Germany.
FAU - Schnell, E
AU  - Schnell E
FAU - Verhage, M
AU  - Verhage M
FAU - Tzonopoulos, T
AU  - Tzonopoulos T
FAU - Nicoll, R A
AU  - Nicoll RA
FAU - Janz, R
AU  - Janz R
FAU - Malenka, R C
AU  - Malenka RC
FAU - Geppert, M
AU  - Geppert M
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 Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA Primers)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (rabphilin-3A)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rab3 GTP-Binding Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Brain/*physiology
MH  - Cerebral Cortex/physiology
MH  - Cloning, Molecular
MH  - DNA Primers
MH  - Exocytosis
MH  - GTP-Binding Proteins/deficiency/genetics/*metabolism/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Neurological
MH  - Nerve Tissue Proteins/deficiency/genetics/*metabolism/*physiology
MH  - Neuronal Plasticity
MH  - Neurotransmitter Agents/*metabolism
MH  - Polymerase Chain Reaction
MH  - Restriction Mapping
MH  - Subcellular Fractions/physiology
MH  - Synapses/physiology
MH  - Synaptic Vesicles/*physiology
MH  - Vesicular Transport Proteins
MH  - *rab GTP-Binding Proteins
MH  - rab3 GTP-Binding Proteins
PMC - PMC6783077
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Jul 15;19(14):5834-46.