Iled-coil structures of about 1000 amino acids. A present hypothesis PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19861958 proposes that these regions might convey cytoskeletal interactions that in vertebrates could be mediated by Piccolo and/ or Bassoon. Knock-down by RNAi or deletion of the brp gene leads to loss of the presynaptic dense projections, reduction of calcium channel density, severe defects in synaptic transmission, and altered short-term plasticity. Stimulated emission depletion microscopy using the monoclonal antibody nc82 which recognizes a C-terminal 
epitope of BRP revealed that BRP forms a donut-shaped ring centered at active zones. No information is as yet available on the molecular mechanisms of AZ assembly in Drosophila while in vertebrates several active zone proteins are transported to the presynaptic terminal in the form of active zone precursor vesicles termed Piccolo transport vesicles . Presumably, many more types of transport vesicles will be found, considering the complexity of vesicles observed near nascent active zones. Drosophila SRPK79D Author Summary Neurons communicate through release of ONX-0914 biological activity neurotransmitters at specialized contacts called synapses. Modulation of synaptic transmission likely underlies all higher brain function including feature abstraction, learning and memory, and cognition. The complex molecular machinery that regulates neurotransmitter release has been conserved in evolution but is still incompletely understood. Using the genetic model organism Drosophila, we recently discovered a protein of the presynaptic ribbon that was called Bruchpilot because flies with reduced amounts of this protein cannot fly. We now screened various Drosophila PCI32765 mutants for changes in tissue localization of Bruchpilot and discovered a gene that codes for an enzyme which is similar to mammalian kinases that phosphorylate splicing factors and may colocalize with Bruchpilot at the synapse. Larval nerves of mutants for this gene contain conspicuous accumulations of Bruchpilot that correspond to extensive electron-dense ribbon-like agglomerates surrounded by vesicles. While general axonal transport and basic synaptic transmission at larval nerve-muscle synapses are not affected, adult mutants show reduced life span and impaired flight and walking. The substrate for this kinase and its role in maintaining brain function must now be identified. Its discovery raises important questions about the function of homologous proteins in mammals including humans. Posttranslational modification of proteins of the CAZ has been suggested to be an important mechanism of synaptic modulation. For example, mammalian serine/threonine kinase SAD-B is associated with synaptic vesicles and with CAZ, it phosphorylates RIM but not Munc13, and interference with SAD-B targeting inhibits synaptic transmission. The Drosophila SAD homologue apparently has not yet been characterized. By screening for mutants with altered tissue distribution of BRP we now have identified a kinase presumably associated specifically with presynaptic active zones of Drosophila. It shows high homology to mammalian SR protein kinases. SR proteins are highly conserved phosphoproteins involved in the regulation of constitutive and alternative splicing. SR proteins exhibit one or two N-terminal RNA-binding regions termed RRM, as well as a serine/ arginine rich C-terminal domain which is required for protein-protein interactions affecting cellular localization and regulation of splicing. The genome of Drosophila melanogaster.Iled-coil structures of about 1000 amino acids. A present hypothesis PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19861958 proposes that these regions might convey cytoskeletal interactions that in vertebrates could be mediated by Piccolo and/ or Bassoon. Knock-down by RNAi or deletion of the brp gene leads to loss of the presynaptic dense projections, reduction of calcium channel density, severe defects in synaptic transmission, and altered short-term plasticity. Stimulated emission depletion microscopy using the monoclonal antibody nc82 which recognizes a C-terminal epitope of BRP revealed that BRP forms a donut-shaped ring centered at active zones. No information 
is as yet available on the molecular mechanisms of AZ assembly in Drosophila while in vertebrates several active zone proteins are transported to the presynaptic terminal in the form of active zone precursor vesicles termed Piccolo transport vesicles . Presumably, many more types of transport vesicles will be found, considering the complexity of vesicles observed near nascent active zones. Drosophila SRPK79D Author Summary Neurons communicate through release of neurotransmitters at specialized contacts called synapses. Modulation of synaptic transmission likely underlies all higher brain function including feature abstraction, learning and memory, and cognition. The complex molecular machinery that regulates neurotransmitter release has been conserved in evolution but is still incompletely understood. Using the genetic model organism Drosophila, we recently discovered a protein of the presynaptic ribbon that was called Bruchpilot because flies with reduced amounts of this protein cannot fly. We now screened various Drosophila mutants for changes in tissue localization of Bruchpilot and discovered a gene that codes for an enzyme which is similar to mammalian kinases that phosphorylate splicing factors and may colocalize with Bruchpilot at the synapse. Larval nerves of mutants for this gene contain conspicuous accumulations of Bruchpilot that correspond to extensive electron-dense ribbon-like agglomerates surrounded by vesicles. While general axonal transport and basic synaptic transmission at larval nerve-muscle synapses are not affected, adult mutants show reduced life span and impaired flight and walking. The substrate for this kinase and its role in maintaining brain function must now be identified. Its discovery raises important questions about the function of homologous proteins in mammals including humans. Posttranslational modification of proteins of the CAZ has been suggested to be an important mechanism of synaptic modulation. For example, mammalian serine/threonine kinase SAD-B is associated with synaptic vesicles and with CAZ, it phosphorylates RIM but not Munc13, and interference with SAD-B targeting inhibits synaptic transmission. The Drosophila SAD homologue apparently has not yet been characterized. By screening for mutants with altered tissue distribution of BRP we now have identified a kinase presumably associated specifically with presynaptic active zones of Drosophila. It shows high homology to mammalian SR protein kinases. SR proteins are highly conserved phosphoproteins involved in the regulation of constitutive and alternative splicing. SR proteins exhibit one or two N-terminal RNA-binding regions termed RRM, as well as a serine/ arginine rich C-terminal domain which is required for protein-protein interactions affecting cellular localization and regulation of splicing. The genome of Drosophila melanogaster.