title: Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2.
abstract: The precise regulation of synapse maintenance is critical to the development and function of neuronal circuits. Using an in vivo RNAi screen targeting the Drosophila kinome and phosphatome, we identify 11 kinases and phosphatases controlling synapse stability by regulating cytoskeletal, phospholipid, or metabolic signaling. We focus on casein kinase 2 (CK2) and demonstrate that the regulatory (β) and catalytic (α) subunits of CK2 are essential for synapse maintenance. CK2α kinase activity is required in the presynaptic motoneuron, and its interaction with CK2β, mediated cooperatively by two N-terminal residues of CK2α, is essential for CK2 holoenzyme complex stability and function in vivo. Using genetic and biochemical approaches we identify Ankyrin2 as a key presynaptic target of CK2 to maintain synapse stability. In addition, CK2 activity controls the subcellular organization of individual synaptic release sites within the presynaptic nerve terminal. Our study identifies phosphorylation of structural synaptic components as a compelling mechanism to actively control the development and longevity of synaptic connections.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bulat
authors.forename: Melanie
authors.initials: M
authors.lastname: Rast
authors.forename: Jan
authors.initials: J
authors.lastname: Pielage
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D029721:Drosophila Proteins; D010743:Phospholipids; D047390:Casein Kinase II; C585873:CkIIalpha protein, Drosophila; D010744:Phosphoric Monoester Hydrolases