Drosophila melanogaster Scramblases modulate synaptic transmission.
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.
Acharya
Usha
U
Laboratory of Protein Dynamics and Signaling, National Cancer Institute Frederick, Frederick, MD 21702, USA.
Edwards
Michael Beth
MB
Jorquera
Ramon A
RA
Silva
Hugo
H
Nagashima
Kunio
K
Labarca
Pedro
P
Acharya
Jairaj K
JK
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics; D030561:Databases, Nucleic Acid; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D005089:Exocytosis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007814:Larva / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000002:abnormalities* / Q000201:enzymology* / Q000235:genetics; D018377:Neurotransmitter Agents / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013570:Synaptic Membranes / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure
D029721:Drosophila Proteins; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C510773:Scramb1 protein, Drosophila; C510774:Scramb2 protein, Drosophila