Time- and polarity-dependent proteomic changes associated with homeostatic scaling at central synapses.

Christoph T Schanzenbächer,Erin M Schuman,Julian D Langer

doi:10.7554/elife.33322

Christoph T Schanzenbächer, Erin M Schuman + Show 1 more

Open Access

https://doi.org/10.7554/elife.33322

Copy DOI

Abstract

In homeostatic scaling at central synapses, the depth and breadth of cellular mechanisms that detect the offset from the set-point, detect the duration of the offset and implement a cellular response are not well understood. To understand the time-dependent scaling dynamics we treated cultured rat hippocampal cells with either TTX or bicucculline for 2 hr to induce the process of up- or down-scaling, respectively. During the activity manipulation we metabolically labeled newly synthesized proteins using BONCAT. We identified 168 newly synthesized proteins that exhibited significant changes in expression. To obtain a temporal trajectory of the response, we compared the proteins synthesized within 2 hr or 24 hr of the activity manipulation. Surprisingly, there was little overlap in the significantly regulated newly synthesized proteins identified in the early- and integrated late response datasets. There was, however, overlap in the functional categories that are modulated early and late. These data indicate that within protein function groups, different proteomic choices can be made to effect early and late homeostatic responses that detect the duration and polarity of the activity manipulation.

Highlights

IntroductionMany variables like pH, ion concentration and temperature are under homeostatic control
In biological systems, many variables like pH, ion concentration and temperature are under homeostatic control
The methionine content of our AHA-labeled proteins was not different compared to a global proteome (Rattus norvegicus, UniProtKB database) as, on average, 2.42 and 2.40 Met residues are present per 100 amino acids, respectively (Figure 1—figure supplement 1I)

Summary

Introduction

Many variables like pH, ion concentration and temperature are under homeostatic control. A form of homeostatic plasticity, allows neurons to adjust globally the strengths of their synapses up or down to stabilize specific neuronal functions in response to an offset from a setpoint (Turrigiano et al, 1998; Davis and Goodman, 1998; Burrone et al, 2002; Turrigiano, 2012). In homeostatic scaling at central mammalian synapses, there is emerging consensus that one end-point effector mediating both the enhanced and reduced response following a prolonged activity manipulation is the AMPA-type glutamate receptor (Cingolani et al, 2008; O’Brien et al, 1998; Wierenga et al, 2005; Thiagarajan et al, 2005; Sutton et al, 2006; Gainey et al, 2009, 2015)

Methods

Results

Conclusion