LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor.
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.
Eaton
Benjamin A
BA
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143, USA.
Davis
Graeme W
GW
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
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