The mechanism of the neurotransmitter release in growth cones

Abstract

The growth cone is considered the precursor of the presynaptic terminal. To elucidate the minimal molecular machinery required for exocytosis, we examined the characteristics of α‐latrotoxin‐induced exocytosis in growth cones. In isolated growth cones (IGC), neurotransmitters were released in a SNARE‐dependent manner, but rab3A cycling was blocked. By supplying rabphilin, a rab3A acceptor found in low levels in IGC, the IGC obtained as high an exocytotic efficiency as adult synaptosomes, and the complete GDP‐GTP conversion of rab3A occurred on growth cone vesicles (GCV). GCVs bound SNAREs but not NSF or α‐SNAP; whereas in the rabphilin‐supplied IGC, GCVs recruited both NSF and α‐SNAP, to form the SNARE‐NSF‐SNAP complex. These results suggest that rab3A cycling is dependent upon the accumulation of rabphilin and is completed later than the SNARE mechanism, and that rabphilin is involved in determining the efficiency of exocytosis by modifying the SNARE mechanism. J. Neurosci. Res. 60:743–753, 2000. © 2000 Wiley‐Liss, Inc.

The expression pattern and assembly profile of synaptic membrane proteins in ribbon synapses of the developing mouse retina

“…Vesicle clusters have already been observed by electron-microscopic studies in the retina (Olney 1968a(Olney , 1968b and probably correspond to growth cone vesicles also observed in other experimental systems (Igarashi et al 1996(Igarashi et al , 1997(Igarashi et al , 2000. Ribbon synapse formation is a multistep process which starts with a non-synchronized expression of synaptic membrane proteins and their targeting to immature ribbon synapses.…”

“…These synaptic maturation events could include the synaptic ribbons and ribbon-specific proteins, e.g., RIBEYE (Schmitz et al 2000), and are probably complemented by general maturation processes, e.g., complex formation between synaptic proteins, post-translational modifications (Becher et al 1999a(Becher et al , 1999bChapman et al 1996;Garcia et al 1995;Gundersen et al 1994;Hess et al 1992;Lane and Liu 1997;Littleton et al 1995;Igarashi et al 1997Igarashi et al , 2000Veit et al 1996Veit et al , 2000 and activity-dependent functional and structural changes. These synaptic maturation events could include the synaptic ribbons and ribbon-specific proteins, e.g., RIBEYE (Schmitz et al 2000), and are probably complemented by general maturation processes, e.g., complex formation between synaptic proteins, post-translational modifications (Becher et al 1999a(Becher et al , 1999bChapman et al 1996;Garcia et al 1995;Gundersen et al 1994;Hess et al 1992;Lane and Liu 1997;Littleton et al 1995;Igarashi et al 1997Igarashi et al , 2000Veit et al 1996Veit et al , 2000 and activity-dependent functional and structural changes.…”

Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons

“…A novel mechanism for presynaptic targeting of Ca 2+ channels by CRMP-2 It has been established that Ca 2+ influx via presynaptic Ca 2+ channels is crucial for the release of neurotransmitters at the nerve terminal (Augustine, 2001;Catterall and Few, 2008;Stanley, 1997). Functional Ca 2+ channels contributing to transmitter release have been observed very early during synaptogenesis (Hall and Sanes, 1993;Igarashi et al, 2000;Poo et al, 1985;Vigers and Pfenninger, 1991), suggesting that precursors to synaptic terminals (i.e. growth cones) contain the synaptic vesicle machinery obligatory for synaptic transmission.…”

“…In addition to a key role in triggering transmitter release, Ca 2+ signals contribute to the dynamics of neuronal growth cones (Spitzer, 1995). That Ca 2+ channels are present on growth cones (Soeda et al, 1997;Soeda et al, 1998) and support transmitter release (Hirning et al, 1988;Igarashi et al, 2000;Westenbroek et al, 1992) suggests that this 'pre' synapse-like structure is endowed with all the proteins necessary for vesicular release. However, it remains unclear as to how these Ca 2+ channels are targeted to release sites in growth cones.…”

Exocytic and endocytic membrane trafficking in axon development

“…If the diffusion radius of BDNF is sufficiently shorter than growth cone width, one can speculate that asymmetric exocytosis evoked by such an attractive cue causes activation of the BDNF autocrine loop on one side of the growth cone only, resulting in attractive turning. Similar autocrine mechanism might also be applicable for a range of neurotransmitters including acetylcholine, glutamate, and c-aminobutyric acid (GABA) because growth cones can release and respond to them (Young & Poo 1983;Zheng et al 1994Zheng et al , 1996Tatsumi et al 1995;Soeda et al 1997;Igarashi et al 2000).…”