LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor

Neuron. 2005 Sep 1;47(5):695-708. doi: 10.1016/j.neuron.2005.08.010.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Depolymerizing Factors
  • Animals
  • Axons / physiology
  • Blotting, Northern
  • Bone Morphogenetic Protein Receptors, Type II
  • Cytoskeleton / physiology
  • DNA-Binding Proteins / physiology
  • Drosophila
  • Electrophysiology
  • Microfilament Proteins / metabolism
  • Microtubules / physiology
  • Motor Neurons / physiology
  • Mutation / physiology
  • Myosin Heavy Chains / metabolism
  • Neuromuscular Junction / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Receptors, Presynaptic / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Smad Proteins
  • Synapses / physiology*
  • Trans-Activators / physiology

Substances

  • Actin Depolymerizing Factors
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Receptors, Presynaptic
  • Smad Proteins
  • Trans-Activators
  • wound-inducible transcript 3.0, rat
  • PDIK1L protein, human
  • Protein-Serine-Threonine Kinases
  • Bone Morphogenetic Protein Receptors, Type II
  • Myosin Heavy Chains