On the chloride dependence of vesicular glutamate transport

Abstract

the recruitment of specific cargo, curving of membranes to overcome energetic barriers during the formation of a membrane bud, and finally cleave off the vesicle membrane area by fission. In fusion events a donor vesicle will be directed to a target site. Lipids and protein receptors are involved in the correct trafficking and then make such a vesicle fusion competent by docking and priming. Finally the energy barrier to fuse two lipid membranes has to be overcome, which is again greatly facilitated by special proteins. Characteristic, not only to the fusion event, but also to the fission, is the non-leaky nature of these processes. The luminal contents never mix with the cytosol.The transport of solutes across the lumen is mediated by various ion pumps, channels and transporters that specifically catalyze the transfer of ions, organic molecules and even protein chains.The chemical transmission of signals between neurons, or neurons and other target cells is essentially built on the above mentioned basic features of the secretory and endocytic pathways. In the billions of neurons that comprise the human brain secretory and endocytic events at the contact points of neurons, the synapses, have reached a remarkable degree of specialization and speed that gives rise to the sensory and cognitive abilities that are characteristic for the CNS. Albeit resembling secretory processes in general, the chemical transmission at the synapse is unique due to its enourmous speed and synchronization which makes it possible to encode a message from one neuron to another in high temporal resolution. Since the neurotransmission is based on the repetitive fusion of a high number of vesicles with the plasma membrane, it is mandatory that the vesicles are regenerated by recycling at the restricted and isolated area of the synaptic terminal in order to refill the pool of transmitter-storing vesicles. The synaptic transmission is therefore a highly regulated interplay between exocytic and endocytic events in a small area of the cell that is specialized on speed and synchrony. This cycle of exocytosis and endocytosis at the synapse that underlies the quantal transmission of signals has therefore been termed synaptic vesicle cycle (Sudhof, 2004).Since the work of Katz and colleagues (Del Castillo and Katz, 1956), it is known that the neurotransmission is encoded in discrete packages of neurotransmitters, the quanta. These packages are the contents of synaptic vesicles (SVs), organelles that store the neurotransmitter which is released into the the synaptic cleft to diffuse to receptors on the postsynaptic membrane. The quantal release and the identification of SVs as the storage pyrophosphate (PP i ) to pump protons) in yeast vacuolar membranes (Hirata et al., 2000).The V-PPase provided the proton electrochemical gradient for ATP synthesis by the V-ATPase. However, normally the equilibrium of ATP / ADP+P i in the cytosol would prevent the synthesis of ATP, despite the fact that the V-ATPase itself is providing Δμ H+ . et al., 2004;Wojcik e...