Dynamic control of excitatory synapse development by a Rac1 GEF/GAP regulatory complex.

The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development.

Cytoskeletal mechanisms for synaptic potentiation.

Excitatory synaptic transmission takes place at actin-rich protrusions called dendritic spines. Strong synaptic input activates NMDA-type glutamate receptors and induces calcium flux into these structures, initiating a program of cytoskeletal rearrangement that results in larger spines with stronger synapses. These changes in synaptic strength are thought to be the primary cellular mechanism underlying learning and memory.

RasGRF2 Rac-GEF activity couples NMDA receptor calcium flux to enhanced synaptic transmission.

Dendritic spines are the primary sites of excitatory synaptic transmission in the vertebrate brain, and the morphology of these actin-rich structures correlates with synaptic function. Here we demonstrate a unique method for inducing spine enlargement and synaptic potentiation in dispersed hippocampal neurons, and use this technique to identify a coordinator of these processes; Ras-specific guanine nucleotide releasing factor 2 (RasGRF2). RasGRF2 is a dual Ras/Rac guanine nucleotide exchange factor (GEF) that is known to be necessary for long-term potentiation in situ.

The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites.

Excitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation.

Histone deacetylase inhibition-mediated differentiation of RGC-5 cells and interaction with survival.

Purpose: The acetylation state of histones is modulated by histone deacetylase (HDAC) and histone acetyltransferase and is an important component in regulating gene transcription, including neuronal differentiation. The authors studied the relationship between histone acetylation and the differentiation and survival of the RGC-5 cell line and compared it with nontranscriptional-dependent differentiation with staurosporine.

Methods: The retinal ganglion cell line RGC-5 was treated with trichostatin A (TSA), other HDAC inhibitors, and staurosporine; differentiation, neuritogenesis, neurotrophic factor dependence, and dependence on RNA transcription were assessed.