RT Journal Article SR Electronic T1 Rabphilin Knock-Out Mice Reveal That Rabphilin Is Not Required for Rab3 Function in Regulating Neurotransmitter Release JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5834 OP 5846 DO 10.1523/JNEUROSCI.19-14-05834.1999 VO 19 IS 14 A1 Oliver M. Schlüter A1 Eric Schnell A1 Matthijs Verhage A1 Thanos Tzonopoulos A1 Roger A. Nicoll A1 Roger Janz A1 Robert C. Malenka A1 Martin Geppert A1 Thomas C. Südhof YR 1999 UL http://www.jneurosci.org/content/19/14/5834.abstract 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 C2 domains, which could function as Ca2+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.