TY - JOUR
T1 - LIM kinase1 controls synaptic stability downstream of the type II BMP receptor
AU - Eaton, Benjamin A.
AU - Davis, Graeme W.
N1 - Funding Information:
The authors would like to gratefully thank the following individuals for the gifts of the indicated fly stocks: medea 2 and medea 4 , from Laurel Raftery; gbb 2 , UAS-gbb 99 , and gbb 1 , from Brian McCabe; UAS-DAD, from Tom Kornberg; UAS-wit cDNA (full-length) and UAS-wit cDNA (dCT), from Michael O’Connor; UAS-DLIMK1 (wt) and UAS-DLIMK1(KI), from Tadashi Uemura; and UAS-SSH wt 29 , UAS-SSH CS 11 , and UAS-tsr S3A , from Julian Ng. The authors also thank Michael O’Connor, for the pACp-Wit-HA plasmid, and Tadashi Uemura, for the pUAST-HA-DLIMK1 plasmid. The authors thank Mario Lioubin and Jessica Tierney, for technical assistance, and Mark Von Zastrow, Robert Edwards, Jan Pielage, and Kira Poskanzer, for comments on earlier versions of the manuscript. This work was supported by an NIH National Research Service Award to B.A.E. and NIH grant # NS047342 to G.W.D.
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2005.08.010
DO - 10.1016/j.neuron.2005.08.010
M3 - Article
C2 - 16129399
AN - SCOPUS:23944519706
SN - 0896-6273
VL - 47
SP - 695
EP - 708
JO - Neuron
JF - Neuron
IS - 5
ER -