SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3.

Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo. Following neuronal stimulation, CPEB3 is converted into an active form that promotes the translation of target mRNAs, and this is associated with a decrease of SUMOylation and an increase of aggregation. A chimeric CPEB3 protein fused to SUMO cannot form aggregates and cannot activate the translation of target mRNAs. These findings suggest a model whereby SUMO regulates translation of mRNAs and structural synaptic plasticity by modulating the aggregation of the prion-like protein CPEB3.

Is depression with atypical features associated with trauma history?

OBJECTIVE: Although studies have linked childhood trauma to depression resembling the atypical subtype, a majority of these studies did not use DSM-IV criteria for atypical features nor assess trauma both before and after depression onset. This study examined the relationship between atypical depression and lifetime trauma with the hypothesis that atypically depressed patients would report a higher number of trauma exposures than nonatypically depressed patients. METHOD: Raters blind to depressive subtype investigated trauma history by reviewing the Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) posttraumatic stress disorder modules and social history sections in charts of depressed outpatients who had participated in treatment studies between 1985 and 2010. Rates of trauma both before and after depression onset were compared for 292 depressed patients with and without DSM-IV-defined atypical features using χ2 tests and binary logistic regressions. This chart review was conducted from 2009 to 2011. RESULTS: Lifetime trauma was reported significantly more often by depressed patients with atypical features than by those without (P < .001). Patients with atypical features reported significantly more traumatic experiences both prior to (P = .012) and following (P = .015) depression onset. When sex and age at onset or duration of depression were used as covariates, depressive subtype was a significant predictor of reported trauma both prior to (P = .028) and following (P = .011) depression onset. CONCLUSIONS: These results suggest that a relationship exists between atypical depression and lifetime trauma that may be more complex than the etiologic pathways outlined in prior research. Rather, trauma and atypical depression may be interrelated throughout life.