The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development.
The formation and plasticity of synaptic connections rely on regulatory interactions between pre- and postsynaptic cells. We show that the Drosophila heparan sulfate proteoglycans (HSPGs) Syndecan (Sdc) and Dallylike (Dlp) are synaptic proteins necessary to control distinct aspects of synaptic biology. Sdc promotes the growth of presynaptic terminals, whereas Dlp regulates active zone form and function. Both Sdc and Dlp bind at high affinity to the protein tyrosine phosphatase LAR, a conserved receptor that controls both NMJ growth and active zone morphogenesis. These data and double mutant assays showing a requirement of LAR for actions of both HSPGs lead to a model in which presynaptic LAR is under complex control, with Sdc promoting and Dlp inhibiting LAR in order to control synapse morphogenesis and function.
Department of Cell Biology and Program in Neuroscience, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Karl G
KG
Johnson
Alan P
AP
Tenney
Aurnab
A
Ghose
April M
AM
Duckworth
Misao E
ME
Higashi
Karen
K
Parfitt
Oana
O
Marcu
Timothy R
TR
Heslip
J Lawrence
JL
Marsh
Thomas L
TL
Schwarz
John G
JG
Flanagan
David
D
Van Vactor
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D003164:Competitive Bidding / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D020439:Growth Cones / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007814:Larva / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008954:Models, Biological; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011956:Receptors, Cell Surface / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D053667:Syndecans; D014162:Transfection / Q000379:methods
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092744:ENA-VASP proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D053667:Syndecans; D006735:Horseradish Peroxidase; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2