How Does a Vesicle Know It Is Full?

Abstract

Expression of the VAChT may provide a way to regulate quantal size at the NMJ. By changing the area of postsynaptic membrane saturated with ACh (Bartol et al. 1991xBartol, T.M Jr., Land, B.R, Salpeter, E.E, and Salpeter, M.M. Biophys. J. 1991; 59: 1290–1307Abstract | Full Text PDF | PubMedSee all ReferencesBartol et al. 1991), alteration in the amount of transmitter in a vesicle is an important determinant of quantal size. The coordinated expression of the VAChT and choline acetyltransferase offers a convenient way for the neuron to control ACh metabolism, and the results of Song et al. show that direct manipulations of VAChT expression can change the quantal size in immature NMJs. Labeling studies predict four VAChTs will be found on each vesicle (Parsons et al. 1993xParsons, S.M, Prior, C, and Marshall, I.G. Int. Rev. Neurobiol. 1993; 35: 279–390Crossref | PubMed | Scopus (160)See all ReferencesParsons et al. 1993), but increases or decreases in this number could be used to modulate quantal size. Furthermore, changes in the activity of the VAChT may account for shorter-term regulation of quantal size. Application of insulin leads to an increase in quantal size that is not sensitive to protein synthesis inhibitors, but which is sensitive to vesamicol. Similarly, metabolic differences have been found between populations of cholinergic vesicles from Torpedo; VP2 vesicles have a 4- to 7-fold higher ratio of transport activity to vesamicol receptor levels.Mu-ming Poo and colleagues have found that immature NMJs have a skewed distribution of quantal sizes dominated by small responses, but note that adult NMJ shows a Gaussian distribution of larger quantal sizes (3xEvers, J, Laser, M, Sun, Y.A, Xie, Z.P, and Poo, M.M. J. Neurosci. 1989; 9: 1523–1539PubMedSee all References, 11xSong, H.-j, Ming, G.-l, Fon, E, Bellocchio, E, Edwards, R.H, and Poo, M.-m. Neuron. 1997; 18: 815–826Abstract | Full Text | Full Text PDF | PubMed | Scopus (130)See all References). Previous studies suggested that the skewed distribution in developing synapses was largely the result of underdeveloped ACh packaging (Evers et al. 1989xEvers, J, Laser, M, Sun, Y.A, Xie, Z.P, and Poo, M.M. J. Neurosci. 1989; 9: 1523–1539PubMedSee all ReferencesEvers et al. 1989). Although overexpression of the VAChT in developing NMJ cultures does not by itself lead to a Gaussian distribution of increased quantal sizes, mean quantal size is increased. Regulation of VAChT expression may be a way for the neuron to control quantal size during the development of mature synaptic transmission.