Presynaptic secretion of mind-the-gap organizes the synaptic extracellular matrix-integrin interface and postsynaptic environments.
Mind-the-Gap (MTG) is required during synaptogenesis of the Drosophila glutamatergic neuromuscular junction (NMJ) to organize the postsynaptic domain. Here, we generate MTG::GFP transgenic animals to demonstrate MTG is synaptically targeted, secreted, and localized to punctate domains in the synaptic extracellular matrix (ECM). Drosophila NMJs form specialized ECM carbohydrate domains, with carbohydrate moieties and integrin ECM receptors occupying overlapping territories. Presynaptically secreted MTG recruits and reorganizes secreted carbohydrates, and acts to recruit synaptic integrins and ECM glycans. Transgenic MTG::GFP expression rescues hatching, movement, and synaptogenic defects in embryonic-lethal mtg null mutants. Targeted neuronal MTG expression rescues mutant synaptogenesis defects, and increases rescue of adult viability, supporting an essential neuronal function. These results indicate that presynaptically secreted MTG regulates the ECM-integrin interface, and drives an inductive mechanism for the functional differentiation of the postsynaptic domain of glutamatergic synapses. We suggest that MTG pioneers a novel protein family involved in ECM-dependent synaptic differentiation.
Rushton
Emma
E
Department of Biological Sciences, Vanderbilt Brain Institute, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37235-1634, USA.
Rohrbough
Jeffrey
J
Broadie
Kendal
K
D000818:Animals; D030801:Animals, Genetically Modified; D050260:Carbohydrate Metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016023:Integrins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D002352:Carrier Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D016023:Integrins; C540270:mtg protein, Drosophila