Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Synapse maintenance is critical for neuronal circuit development and function.
• Protein kinases and phosphatases play vital roles in cellular signaling pathways.

Purpose of the Study:

• To identify kinases and phosphatases involved in synapse stability using an in vivo RNAi screen in Drosophila.
• To elucidate the role of casein kinase 2 (CK2) in presynaptic synapse maintenance.

Main Methods:

• Conducted an in vivo RNAi screen of the Drosophila kinome and phosphatome.
• Utilized genetic and biochemical approaches to study CK2 function and its interaction with Ankyrin2.
• Investigated the requirement of CK2 subunits and kinase activity in presynaptic motoneurons.

Main Results:

• Identified 11 kinases and phosphatases regulating synapse stability via cytoskeletal, phospholipid, or metabolic signaling.
• Demonstrated that both regulatory (β) and catalytic (α) subunits of CK2 are essential for synapse maintenance.
• Confirmed Ankyrin2 as a key presynaptic target of CK2, crucial for synapse stability.
• Showed CK2 activity controls the organization of synaptic release sites.

Conclusions:

• Phosphorylation of synaptic components by CK2 is a key mechanism for controlling synapse development and longevity.
• CK2 holoenzyme complex stability, dependent on CK2α-CK2β interaction, is vital for in vivo synaptic function.
• CK2's role extends to regulating the precise subcellular organization of synaptic release sites.