Selective 14-3-3 γ Upregulation Promotes Beclin-1-LC3-Autophagic Influx via β-Catenin Interaction in Starved Neurons In Vitro and In Vivo.

Selective 14-3-3γ Upregulation Promotes Beclin-1-LC3-Autophagic Influx via β-Catenin Interaction in Starved Neurons In Vitro and In Vivo. Neurochem Res. 2019 Jan 11;: Authors: Xiong XX, Hu DX, Xu L, Lin H, Zhang Y, Li CY, Chen XQ Abstract Lack of blood or glucose supply is the most common pathological factor in the brain. To cope with such an energy stress, initiating programmed autophagic processes in neurons is required. However, the mechanisms controlling neuronal autophagy during starvation remain far from clear. Here, we report an essential role of 14-3-3γ in starvation-activated neuronal autophagic influx signaling and elucidate the underlying mechanism. Double-fluorescent immunostaining demonstrates that 14-3-3γ protein elevation is well co-localized with Beclin-1 and LC3 elevation in cortical neurons in ischemic brains. Starvation treatment activates autophagic influx and upregulates Beclin-1 and only the γ isoform of 14-3-3 in N2a cells and cultured cortical neurons. Suppressing overall 14-3-3 function by difopein overexpression or knocking-out the γ isoform of 14-3-3 is sufficient to abolish starvation-induced Beclin-1 induction and LC3 activation while overexpressing 14-3-3γ but no other 14-3-3 isoform significantly upregulate Beclin-1-LC3 signaling. Upon starvation, 14-3-3γ binds more p-β-catenin but less Beclin-1. Finally, overexpressing 14-3-3γ reactivates β-catenin-suppressed Beclin-1-LC3 signaling in neuron...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research