Abstract
Environmental changes cause stress, Reactive Oxygen Species and unfolded protein accumulation which hamper synaptic activity and trigger cell death. Heat shock proteins (HSPs) assist protein refolding to maintain proteostasis and cellular integrity. Mechanisms regulating the activity of HSPs include transcription factors and posttranslational modifications that ensure a rapid response. HSPs preserve synaptic function in the nervous system upon environmental insults or pathological factors and contribute to the coupling between environmental cues and neuron control of development. We have performed a biased screening in Drosophila melanogaster searching for synaptogenic modulators among HSPs during development. We explore the role of two small-HSPs (sHSPs), sHSP23 and sHSP26 in synaptogenesis and neuronal activity. Both sHSPs immunoprecipitate together and the equilibrium between both chaperones is required for neuronal development and activity. The molecular mechanism controlling HSP23 and HSP26 accumulation in neurons relies on a novel gene (CG1561), which we name Pinkman (pkm). We propose that sHSPs and Pkm are targets to modulate the impact of stress in neurons and to prevent synapse loss.
Highlights
Synaptic dynamics remodel neuronal circuits under stress conditions [1]
The quantification of the active zones revealed that the knockdown of sHsp20, sHsp22, sHsp26, sHsp27, sHsp40 and Hsp90 during development provoked a reduction in synapse number
We tested the effect in synapse number of sHsp23, sHsp26 and Hsp70 overexpression (Fig 1B)
Summary
The Heat Shock Protein family (HSPs) is involved in preserving cellular functions such as stress tolerance, protein folding and degradation, cytoskeleton integrity, cell cycle and cell death [2,3,4,5,6,7]. HSPs are molecular chaperones that represent an intracellular protein quality system to maintain cellular protein homeostasis, preventing aggregation and promoting protein de novo folding or refolding and degradation of misfolded proteins [8]. In Drosophila development small Heat Shock proteins (sHsps) have a specific temporal and spatial pattern of expression [10]. SHsp and sHsp show high expression levels in CNS during development, suggesting a role in neural development [10]
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