19 June 2008. Synaptic remodeling in response to neuronal activity relies on activity-stimulated changes in gene expression, and a new study shows that the regulatory microRNA miR132 is a key player in this pathway. In a report due out this week in PNAS, Soren Impey and Richard Goodman at Oregon Health Sciences University in Portland, Oregon, present evidence that induction of miR132 contributes to dendrite growth after neuronal stimulation via downregulation of the synaptic protein p250GAP.
In the study, first author Gary Wayman and colleagues show that miR132 rises rapidly in hippocampal neurons after synaptic stimulation. Their data indicate that activation of the transcription factor CREB increases miR132 expression, resulting in enhanced dendrite growth. The effect of miR132 on dendrite plasticity is mediated in part by translational repression of the Rho family GTPase activating protein, p250GAP, which is associated with NMDA receptors and regulates dendritic remodeling via the Rac GTPase.
Regulatory microRNAs have been implicated in pathways related to Alzheimer disease, where they can modulate expression of the β-secretase enzyme (see ARF related news story and ARF news story), and in Parkinson disease, where they control dopamine neuron development (see ARF related news story). Along with a recent report linking another microRNA to plasticity at neuromuscular synapses (Simon et al., 2008), the new study adds to a sense that we have glimpsed only the tip of the iceberg when it comes to the roles of microRNA in neuronal function.—Pat McCaffrey.
Wayman GA, Davare M, Ando H, Fortin D, Varlamova O, Cheng HM, Marks D, Obrietan K, Soderling TR Goodman RH, Impey S. An activity-regulated microRNA controls dendritic plasticity by downregulating p250GAP. 2008 June 16. PNAS Early Edition. Abstract