Drosophila melanogaster Scramblases modulate synaptic transmission

• Published in: The Journal of cell biology 2006-04, Vol.173 (1), p.69-82
• Main Authors: Acharya, Usha, Edwards, Michael Beth, Jorquera, Ramon A, Silva, Hugo, Nagashima, Kunio, Labarca, Pedro, Acharya, Jairaj K
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Cell Membrane - enzymology; Cell Membrane - genetics; Cellular biology; Databases, Nucleic Acid; Drosophila melanogaster; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Exocytosis - genetics; Gene Expression Regulation, Enzymologic - genetics; Immunity, Innate - genetics; Insects; Larva - enzymology; Larva - genetics; Larva - growth & development; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Proteins - physiology; Microscopy, Electron, Transmission; Molecular Sequence Data; Mutation; Mutation - genetics; Neuromuscular Junction - abnormalities; Neuromuscular Junction - enzymology; Neuromuscular Junction - genetics; Neurotransmitter Agents - metabolism; Neurotransmitter Agents - secretion; Neurotransmitters; Phospholipid Transfer Proteins - genetics; Phospholipid Transfer Proteins - physiology; Phospholipids - metabolism; Proteins; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Synaptic Membranes - enzymology; Synaptic Membranes - secretion; Synaptic Membranes - ultrastructure; Synaptic Transmission - genetics; Synaptic Transmission - physiology; Synaptic Vesicles - enzymology; Synaptic Vesicles - secretion; Synaptic Vesicles - ultrastructure
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200506159

Scramblases are a family of single-pass plasma membrane proteins, identified by their purported ability to scramble phospholipids across the two layers of plasma membrane isolated from platelets and red blood cells. However, their true in vivo role has yet to be elucidated. We report the generation and isolation of null mutants of two Scramblases identified in Drosophila melanogaster. We demonstrate that flies lacking either or both of these Scramblases are not compromised in vivo in processes requiring scrambling of phospholipids. Instead, we show that D. melanogaster lacking both Scramblases have more vesicles and display enhanced recruitment from a reserve pool of vesicles and increased neurotransmitter secretion at the larval neuromuscular synapses. These defects are corrected by the introduction of a genomic copy of the Scramb 1 gene. The lack of phenotypes related to failure of scrambling and the neurophysiological analysis lead us to propose that Scramblases play a modulatory role in the process of neurotransmission.