Negative regulation of active zone assembly by a newly identified SR protein kinase.
Presynaptic, electron-dense, cytoplasmic protrusions such as the T-bar (Drosophila) or ribbon (vertebrates) are believed to facilitate vesicle movement to the active zone (AZ) of synapses throughout the nervous system. The molecular composition of these structures including the T-bar and ribbon are largely unknown, as are the mechanisms that specify their synapse-specific assembly and distribution. In a large-scale, forward genetic screen, we have identified a mutation termed air traffic controller (atc) that causes T-bar-like protein aggregates to form abnormally in motoneuron axons. This mutation disrupts a gene that encodes for a serine-arginine protein kinase (SRPK79D). This mutant phenotype is specific to SRPK79D and is not secondary to impaired kinesin-dependent axonal transport. The srpk79D gene is neuronally expressed, and transgenic rescue experiments are consistent with SRPK79D kinase activity being necessary in neurons. The SRPK79D protein colocalizes with the T-bar-associated protein Bruchpilot (Brp) in both the axon and synapse. We propose that SRPK79D is a novel T-bar-associated protein kinase that represses T-bar assembly in peripheral axons, and that SRPK79D-dependent repression must be relieved to facilitate site-specific AZ assembly. Consistent with this model, overexpression of SRPK79D disrupts AZ-specific Brp organization and significantly impairs presynaptic neurotransmitter release. These data identify a novel AZ-associated protein kinase and reveal a new mechanism of negative regulation involved in AZ assembly. This mechanism could contribute to the speed and specificity with which AZs are assembled throughout the nervous system.
Johnson
Ervin L
EL
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA.
Fetter
Richard D
RD
Davis
Graeme W
GW
D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000201:enzymology; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D009435:Synaptic Transmission
C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases