This question demands further study, but one possibility is that both CNIHs and TARPs function as auxiliary proteins at synapses. In this scenario, most AMPARs are associated with TARPs, but a larger proportion of intracellular AMPARs are exclusively associated with CNIHs, perhaps when localized to the ER or Golgi. The studies of CNIHs are particularly interesting because the strength of synaptic transmission depends on the number of receptors localized to the synapse; the conductance of each receptor; and the amount of time the receptors conduct current after glutamate binding. That TARPs and CNIHs separately or
together influence the trafficking and function of AMPARs has immediate implications for the modulation of synaptic transmission and may contribute to LTP Anticancer Compound Library and LTD (Kessels and Malinow, 2009). However, the definitive word on whether or how CNIHs contribute to synaptic AMPAR function awaits detailed analysis of cornichon mutants in mice or other organisms. In the last decade,
additional proteins that associate with AMPARs have been identified, starting with C. elegans SOL-1, a CUB-domain transmembrane ERK inhibitor protein that dramatically slows the rate of AMPAR desensitization and increases the rate of recovery from desensitization ( Walker et al., 2006 and Zheng et al., 2004). More recently, CKAMP44 was found to accelerate the rate of AMPAR desensitization ( von Engelhardt et al., 2010), and SynDIG1 regulates the development of excitatory synapses ( Kalashnikova et al., 2010). These are exciting times for the study of synaptic function. We have witnessed tremendous progress as the field has rapidly progressed from a channel-centric view to that of a receptor complex, with channel function modulated by different families of auxiliary proteins. An understanding of how these complexes are assembled, stabilized, and regulated seems essential for a mechanistic understanding of learning and memory. “
suggests that Iodothyronine deiodinase the well-known action of the vesicular proton pump (vATPase) in acidifying synaptic vesicles is perhaps not the entire story of its interesting life. In addition to recent suggestions of its effects on SNARE complex formation and fusion pore formation, now comes evidence that its postexocytic pumping of protons out of the cell accelerates endocytosis. Previous studies have demonstrated an activity-dependent acidification of cytoplasm in cell bodies and dendrites of neurons. The work of Zhang et al. (2010), presented in this issue of Neuron, is the first to measure pH changes in mature nerve terminals resulting from nerve activity. Using a transgenic mouse expressing soluble Yellow Fluorescent Protein (YFP, whose fluorescence is quenched by protons) in its motor nerve terminals, they confirm that repetitive stimulation (50 Hz) produces fast acidification like that observed in cell bodies and dendrites.