Neuroscience. SUMO wrestles the synapse.
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Biomedical subjects
Asim A Beg
Publications and source records attributed to Asim A Beg.
The diacylglycerol-binding protein alpha1-chimaerin regulates dendritic morphology.
The morphological and functional differentiation of neuronal dendrites is controlled through transcriptional programs and cell-cell signaling. Synaptic activity is thought to play an important role in the maturation of dendritic arbors, but the signaling pathways that couple neuronal activity and morphological changes in dendrites are not well understood. We explored the function of alpha1-chimaerin, a neuronal diacylglycerol-binding protein with a Rho GTPase-activating protein domain that inactivates Rac1. We find that stimulation of phospholipase Cbeta-coupled cell surface receptors recruits alpha1-chimaerin to the plasma membrane of cultured hippocampal neurons. We further show that alpha1-chimaerin protein levels are controlled by synaptic activity and that increased alpha1-chimaerin expression results in the pruning of dendritic spines and branches. This pruning activity requires both the diacylglycerol-binding and Rac GTPase-activating protein activity of alpha1-chimaerin. Suppression of alpha1-chimaerin expression resulted in increased process growth from the dendritic shaft and from spine heads. Our data suggest that alpha1-chimaerin is an activity-regulated Rho GTPase regulator that is activated by phospholipase Cbeta-coupled cell surface receptors and contributes to pruning of dendritic arbors.
Animals↗
The GABA nervous system in C. elegans.
GABA neurotransmission requires a specialized set of proteins to synthesize, transport or respond to GABA. This article reviews results from a genetic strategy in the nematode Caenorhabditis elegans designed to identify the genes responsible for these activities. These studies identified mutations in genes encoding five different proteins: the biosynthetic enzyme for GABA, the vesicular GABA transporter, a transcription factor that determines GABA neuron identity, a classic inhibitory GABA receptor and a novel excitatory GABA receptor. This review discusses the strategy employed to identify these genes as well as the conclusions about GABA transmission derived from study of the mutant phenotypes.
Animals↗
EXP-1 is an excitatory GABA-gated cation channel.
Gamma-aminobutyric acid (GABA) mediates fast inhibitory neurotransmission by activating anion-selective ligand-gated ion channels. Although electrophysiological studies indicate that GABA may activate cation-selective ligand-gated ion channels in some cell types, such a channel has never been characterized at the molecular level. Here we show that GABA mediates enteric muscle contraction in the nematode Caenorhabditis elegans via the EXP-1 receptor, a cation-selective ligand-gated ion channel. The EXP-1 protein resembles ionotropic GABA receptor subunits in almost all domains. In the pore-forming domain of EXP-1, however, the residues that confer anion selectivity are exchanged for those that specify cation selectivity. When expressed in Xenopus laevis oocytes, EXP-1 forms a GABA receptor that is permeable to cations and not anions. We conclude that some of the excitatory functions assigned to GABA are mediated by cation channels rather than by anion channels.
Amino Acid Sequence↗