mRNA transport and local translation in dendrites play key roles in use-dependent synaptic modification and in higher-order brain functions. RNG105, an RNA-binding protein, has previously been identified as a component of RNA granules that mediate dendritic mRNA localization and local translation. Here, we demonstrate that RNG105 knock-out in mice reduces the dendritic localization of mRNAs for Na + /K + ATPase (NKA) subunit isoforms (i.e., α3, FXYD1, FXYD6, and FXYD7). The loss of dendritic mRNA localization is accompanied by the loss of function of NKA in dendrites without affecting the NKA function in the soma. Furthermore, we show that RNG105 deficiency affects the formation and maintenance of synapses and neuronal networks. These phenotypes are partly explained by an inhibition of NKA, which is known to influence synaptic functions as well as susceptibility to neurotoxicity. The present study first demonstrates the in vivo role of RNG105 in the dendritic localization of mRNAs and uncovers a novel link between dendritic mRNA localization and the development and maintenance of functional networks.
Connexin43 (Cx43), a major component of astrocytic gap junctions, is abundantly expressed in Bergmann glial cells (BGCs) in the cerebellum, but the function of Cx43 in BGCs is largely unknown. BGCs are specialized astrocytes closely associated with Purkinje cells. Here, we review our recent studies of the role of Cx43 in gap junctional coupling between BGCs and in cerebellar function. We generated Cx43 conditional knockout mice with an S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre), in which there was a significant postnatal loss of Cx43 in BGCs and cerebellar astrocytes. Gap junctional coupling between BGCs measured by dye coupling was virtually abolished in Cx43fl/fl:S100b-Cre mice. Electrophysiologic and behavioral analyses suggested that Cx43-mediated gap junctions and Cx43 hemichannels in BGCs are not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning. These findings raise questions regarding the regional differences in the impact of the loss of Cx43 in the brain.
In recent years, Knowledge about the biochemical nature of proteins involved in the synaptic exocytosis has rapidly increased, and SNARE-hypothesis, which assumes necessity of ATP hydrolysis by NSF protein before membrane fusion, has been proposed to explain sequential processes of exocytosis. However, some recent experimental data do not support the SNARE-hypothesis. New model (the zipper model) does not assume ATP hydrolysis before membrane fusion, rather it assume membrane fusion elicited by protein-protein interaction among syntaxin, SNAP-25 and VAMP. However, there remain many problems to be solved.
The Rab3 GDP/GTP exchange protein (Rab3 GEP) activates the Rab3 small GTP-binding protein (G protein) family, including Rab3A that is an important member controlling synaptic vesicle trafficking. Here, we examined the role of Rab3 GEP in regulating neurotransmitter release in autapses of mouse hippocampal neurons in culture. The release probability was markedly reduced in Rab3 GEP−/− neurons, whereas the readily releasable pool size was not different between WT and Rab3 GEP−/− neurons, indicating that Rab3 GEP up-regulates a postdocking step of synaptic exocytosis. Because Rab3A reportedly down-regulates Ca 2+ -triggered fusion of synaptic vesicles, these results provide evidence for a role of Rab3 GEP in the postdocking process distinct from Rab3A activation.
