Syndapin promotes formation of a postsynaptic membrane system in Drosophila.
Syndapins belong to the F-BAR domain protein family whose predicted functions in membrane tubulation remain poorly studied in vivo. At Drosophila neuromuscular junctions, syndapin is associated predominantly with a tubulolamellar postsynaptic membrane system known as the subsynaptic reticulum (SSR). We show that syndapin overexpression greatly expands this postsynaptic membrane system. Syndapin can expand the SSR in the absence of dPAK and Dlg, two known regulators of SSR development. Syndapin's N-terminal F-BAR domain, required for membrane tubulation in cultured cells, is required for SSR expansion. Consistent with a model in which syndapin acts directly on postsynaptic membrane, SSR expansion requires conserved residues essential for membrane binding in vitro. However, syndapin's Src homology (SH) 3 domain, which negatively regulates membrane tubulation in cultured cells, is required for synaptic targeting and strong SSR induction. Our observations advance knowledge of syndapin protein function by 1) demonstrating the in vivo relevance of membrane remodeling mechanisms suggested by previous in vitro and structural analyses, 2) showing that SH3 domains are necessary for membrane expansion observed in vivo, and 3) confirming that F-BAR proteins control complex membrane structures.
Kumar
Vimlesh
V
Smurfit Institute of Genetics and Trinity College Institute of Neuroscience, University of Dublin Trinity College, Ireland. kumarv@tcd.ie
Fricke
Robert
R
Bhar
Debjani
D
Reddy-Alla
Suneel
S
Krishnan
K S
KS
Bogdan
Sven
S
Ramaswami
Mani
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport
D015415:Biomarkers; D002352:Carrier Proteins; D029721:Drosophila Proteins; C540273:Synd protein, Drosophila