Abstract
In a genetic screen for genes that control synapse development, we have identified spinster (spin), which encodes a multipass transmembrane protein. spin mutant synapses reveal a 200% increase in bouton number and a deficit in presynaptic release. We demonstrate that spin is expressed in both nerve and muscle and is required both pre- and postsynaptically for normal synaptic growth. We have localized Spin to a late endosomal compartment and present evidence for altered endosomal/lysosomal function in spin. We also present evidence that synaptic overgrowth in spin is caused by enhanced/misregulated TGF-beta signaling. TGF-beta receptor mutants show dose-dependent suppression of synaptic overgrowth in spin. Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth. We present a model for synaptic growth control with implications for the etiology of lysosomal storage and neurodegenerative disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Compartmentation / genetics
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Cell Differentiation / genetics*
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Drosophila Proteins / deficiency*
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Drosophila Proteins / genetics
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Drosophila melanogaster / cytology
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Drosophila melanogaster / growth & development*
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Drosophila melanogaster / metabolism
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Endosomes / metabolism*
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Female
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Gene Expression Regulation, Developmental / genetics
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HeLa Cells
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Humans
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Hypertrophy / genetics
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Hypertrophy / metabolism
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Hypertrophy / physiopathology
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Lysosomes / metabolism
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Male
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Membrane Proteins / deficiency*
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Membrane Proteins / genetics
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Muscle, Skeletal / abnormalities
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Muscle, Skeletal / growth & development
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Muscle, Skeletal / innervation
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Mutation / genetics
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Nervous System / cytology
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Nervous System / growth & development*
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Nervous System / metabolism
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Neuromuscular Junction / abnormalities
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Neuromuscular Junction / growth & development
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Neuromuscular Junction / pathology
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / pathology
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Presynaptic Terminals / ultrastructure
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Synaptic Transmission / genetics
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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Drosophila Proteins
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Membrane Proteins
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Transforming Growth Factor beta
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spin protein, Drosophila