title: Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at theDrosophilaNeuromuscular Junction.
abstract: Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at theDrosophilaneuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons. We find that Shv physically and genetically interacts with βPS integrin. Furthermore, Shv is secreted during intense, but not mild, neuronal activity to acutely activate integrin signaling, induce synaptic bouton enlargement, and increase postsynaptic glutamate receptor abundance. Consequently, loss of Shv prevents activity-induced synapse maturation and abolishes post-tetanic potentiation, a form of synaptic plasticity. Our data identify Shv as a novel trans-synaptic signal secreted upon intense neuronal activity to promote synapse remodeling through integrin receptor signaling.SIGNIFICANCE STATEMENTThe ability of neurons to rapidly modify synaptic structure in response to neuronal activity, a process called activity-induced structural remodeling, is crucial for neuronal development and complex brain functions. The molecular players that are important for this fundamental biological process are not well understood. Here we show that the Shriveled (Shv) protein is required during development to maintain normal synaptic growth. We further demonstrate that Shv is selectively released during intense neuronal activity, but not mild neuronal activity, to acutely activate integrin signaling and trigger structural modifications at theDrosophilaneuromuscular junction. This work identifies Shv as a key modulator of activity-induced structural remodeling and suggests that neurons use distinct molecular cues to differentially modulate synaptic growth and remodeling to meet synaptic demand.
authors.affiliation: Zilkha Neurogenetic Institute and.|Neuroscience Graduate Program, University of Southern California, Los Angeles, California 90089.
authors.forename: Joo Yeun
authors.identifier: 0000-0001-6616-5594
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Zilkha Neurogenetic Institute and.
authors.forename: Junhua
authors.identifier: 0000-0001-5817-8870
authors.initials: J
authors.lastname: Geng
authors.affiliation: Zilkha Neurogenetic Institute and.
authors.forename: Juhyun
authors.identifier: 0000-0001-6616-5594
authors.initials: J
authors.lastname: Lee
authors.affiliation: Zilkha Neurogenetic Institute and.
authors.forename: Andrew R
authors.identifier: 0000-0003-4255-4020
authors.initials: AR
authors.lastname: Wang
authors.affiliation: Zilkha Neurogenetic Institute and changkt@usc.edu.|Department of Cell and Neurobiology, Keck School of Medicine, and.|Neuroscience Graduate Program, University of Southern California, Los Angeles, California 90089.
authors.forename: Karen T
authors.identifier: 0000-0001-7619-8170
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila / Q000033:anatomy & histology* / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000619113:Shv protein, Drosophila
keywords: Drosophila; Shriveled; activity-dependent structural remodeling; integrin; neuromuscular junction; synaptic boutons