A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Presynaptic homeostatic plasticity (PHP) is vital for stabilizing synaptic transmission across species.
• PHP's molecular mechanisms, particularly postsynaptic signaling, are not fully understood.

Purpose of the Study:

• To identify the molecular components of the postsynaptic machinery regulating PHP.
• To elucidate the roles of specific signaling molecules in PHP.

Main Methods:

• An electrophysiology-based screen of the *Drosophila* kinome and phosphatome.
• Localization studies of key proteins using microscopy.
• Functional assays to assess the role of identified proteins in PHP.

Main Results:

• Identified a postsynaptic signaling platform involving Phosphoinositide 3-kinase (PI3K)-cII, PI3K-cIII, and the small GTPase Rab11, essential for PHP.
• PI3K-cII localizes to Golgi-derived vesicles and is required for generating PI(3)P, which recruits Rab11 to recycling endosomes.
• A distinct postsynaptic platform subdivision acts as a controller for retrograde trans-synaptic signaling.

Conclusions:

• The study defines a novel postsynaptic signaling platform critical for PHP.
• This platform, involving PI3K-cII, PI3K-cIII, and Rab11, regulates synaptic stability through retrograde signaling.