Rem2 Is an Activity-Dependent Negative Regulator of Dendritic ComplexityIn Vivo

Abstract

A key feature of the CNS is structural plasticity, the ability of neurons to alter their morphology and connectivity in response to sensory experience and other changes in the environment. How this structural plasticity is achieved at the molecular level is not well understood. We provide evidence that changes in sensory experience simultaneously trigger multiple signaling pathways that either promote or restrict growth of the dendritic arbor; structural plasticity is achieved through a balance of these opposing signals. Specifically, we have uncovered a novel, activity-dependent signaling pathway that restricts dendritic arborization. We demonstrate that the GTPase Rem2 is regulated at the transcriptional level by calcium influx through L-VGCCs and inhibits dendritic arborization in cultured rat cortical neurons and in the Xenopus laevis tadpole visual system. Thus, our results demonstrate that changes in neuronal activity initiate competing signaling pathways that positively and negatively regulate the growth of the dendritic arbor. It is the balance of these opposing signals that leads to proper dendritic morphology.

RGK regulation of voltage-gated calcium channels

“…While this study and a similar one that studied Rem2 [51] show a major role for RGKs in altering cell morphology independent of VGCC inhibition, it does not exclude a significant role of VGCC inhibition in contributing to the autistic phenotype. We recently found that Gem inhibited TS currents much more weakly than it did WT Ca v 1.2 currents [53].…”

“…This was demonstrated with a dose-response curve in Xenopus oocytes, where the levels of Gem expression could be carefully titrated by injecting different amounts of Gem RNA. Recently, several reports have focused on the role of RGK proteins, in particular Rem2 [51] and Gem [17], in controlling neuronal morphology. In one study, the effects of the Timothy Syndrome (TS) mutation on dendritic arborization were investigated.…”

“…New RGK binding partners may be identified through yeast two hybrid or other screens. Considering the newly described role of RGK proteins in shaping neuronal morphology [17,51], it would be interesting to identify further links between calcium channels and cytoskeletal reorganization. It would also be interesting to examine whether RGKs interact with synaptic proteins and regulate synaptic transmission, since RGKs have been identified as critical elements for synapse formation [55].…”

Fatherhood alters gene expression within the MPOA

“…Rem2, a gene associated with reduction of dendritic branching but increases in spine density (51,52) was increased in the MPOA of high licking/grooming rats, but only in lactating mothers (not in virgins). This increase peer-reviewed) is the author/funder.…”

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

“…Our data showed that BCG enhanced the dendritic complexity, which served to increase the available surface area for synaptic contact and the capacity for neuronal connectivity. 24 Additionally, BCG increased the dendritic length and number of primary neurites; greater dendritic length and a greater number of primary neurites increase the number of possible synaptic contacts and the information that may be received by a dendrite. 25 Alterations in dendritic characteristics indicated that BCG promoted the process of dendritic development.…”