Excitation-transcription coupling via synapto-nuclear signaling triggers autophagy for synaptic turnover and long-lasting synaptic depression. Issue 11 (2nd November 2021)

• Record Type: Journal Article
• Authors: Pan, Yue; Zhou, Guangjun; Li, Wenwen; He, Xingzhi; Li, Cuicui; Li, Yanjun; Li, Tao; Hu, Hailan; Ma, Huan
• Is Part Of: Autophagy. Volume 17:Issue 11(2021)
• Page Start: 3887
• Page End: 3888
• Publication Date: 2021-11-02
• Subjects: Autophagy -- CREB -- CRTC1 -- excitation-transcription coupling -- L-LTD -- L-LTP -- long-term synaptic plasticity -- LTD -- LTP; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2021.1964888
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: For network rewiring and information storage in the brain, late phase long-term synaptic depression (L-LTD) requires the long-lasting reorganization of cellular resources. We found that activation of GRIN/NMDAR recruits transcription-dependent autophagy for synaptic turnover to support L-LTD. Activity-dependent CRTC1 synapto-nuclear translocation increases nuclear CRTC1 that competes with FXR for binding to CREB; this in turn enhances the direct binding between CRTC1-CREB and macroautophagy/autophagy gene promoters. Synergistic actions of CRTC1-CREB are preferentially turned on by LTD-inducing stimuli and switched off by genetic knockdown of CREB or CRTC1, or acutely activating FXR. Disrupted CRTC1-CREB signaling impairs activity-driven loss of surface GRIA/AMPARs and DLG4/PSD-95, and selectively prevents GRIN/NMDAR-dependent L-LTD, which are rescued by enhancing MTOR-regulated autophagy. These findings suggest a novel mechanism in L-LTD, in which brief synaptic activities recruit long-lasting autophagy through excitation-transcription coupling for ensuing synaptic remodeling.