Small heat shock proteins determine synapse number and neuronal activity during development

Area of Science:

• Neuroscience
• Cell Biology
• Genetics

Background:

• Environmental stress induces Reactive Oxygen Species and protein misfolding, impairing synaptic function and leading to cell death.
• Heat shock proteins (HSPs) are vital chaperones that maintain proteostasis and cellular integrity by aiding protein refolding.
• HSPs are critical for preserving synaptic function against environmental insults and pathological factors, linking environmental cues to neuronal development.

Purpose of the Study:

• To investigate the role of small heat shock proteins (sHSPs) in synaptic development and neuronal activity.
• To identify molecular mechanisms regulating sHSP function in neurons.
• To explore potential therapeutic targets for mitigating stress-induced neuronal damage.

Main Methods:

• Biased screening in Drosophila melanogaster to identify synaptogenic modulators among HSPs.
• Investigating the roles of sHSP23 and sHSP26 in synaptogenesis and neuronal activity.
• Identifying the gene regulating sHSP23 and sHSP26 accumulation using genetic approaches.

Main Results:

• Two small heat shock proteins, sHSP23 and sHSP26, were found to be involved in synaptogenesis and neuronal activity.
• sHSP23 and sHSP26 form complexes, and their balanced interaction is essential for neuronal development and function.
• A novel gene, Pinkman (pkm), was identified as a key regulator of sHSP23 and sHSP26 accumulation in neurons.

Conclusions:

• sHSPs play a significant role in neuronal development and maintaining synaptic function.
• The Pinkman (pkm) gene is a novel regulator of sHSP levels in neurons.
• sHSPs and Pinkman represent potential targets for therapeutic strategies aimed at preventing stress-induced synapse loss and neurodegeneration.