title: LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor.
abstract: Here, we demonstrate that the BMP receptor Wishful Thinking (Wit) is required for synapse stabilization. In the absence of BMP signaling, synapse disassembly and retraction ensue. Remarkably, downstream Smad-mediated signaling cannot fully account for the stabilizing activity of the BMP receptor. We identify LIM Kinase1 (DLIMK1)-dependent signaling as a second, parallel pathway that confers the added synapse-stabilizing activity of the BMP receptor. We show that DLIMK1 binds a region of the Wit receptor that is necessary for synaptic stability but is dispensable for Smad-mediated synaptic growth. A genetic analysis demonstrates that DLIMK1 is necessary, presynaptically, for synapse stabilization, but is not necessary for normal synaptic growth or function. Furthermore, presynaptic expression of DLIMK1 in a wit or mad mutant significantly rescues synaptic stability, growth, and function. DLIMK1 localizes near synaptic microtubules and functions independently of ADF/cofilin, highlighting a novel requirement for DLIMK1 during synapse stabilization rather than actin-dependent axon outgrowth.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Eaton
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D051339:Actin Depolymerizing Factors; D000818:Animals; D001369:Axons / Q000502:physiology; D015152:Blotting, Northern; D052006:Bone Morphogenetic Protein Receptors, Type II; D003599:Cytoskeleton / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004330:Drosophila; D004594:Electrophysiology; D008840:Microfilament Proteins / Q000378:metabolism; D008870:Microtubules / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins; D013569:Synapses / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology
chemical_list: D051339:Actin Depolymerizing Factors; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D017661:Receptors, Presynaptic; D051785:Smad Proteins; D015534:Trans-Activators; C480856:wound-inducible transcript 3.0, rat; C482688:PDIK1L protein, human; D017346:Protein Serine-Threonine Kinases; D052006:Bone Morphogenetic Protein Receptors, Type II; D018995:Myosin Heavy Chains