Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis.
The growth and morphological differentiation of dendrites are critical events in the establishment of proper neuronal connectivity and neural function. One extrinsic factor, BMP7, has been shown to specifically affect dendritic morphogenesis; however, the underlying mechanism by which this occurs is unknown. Here we show that LIM kinase 1 (LIMK1), a key downstream effector of Rho GTPases, colocalizes with the BMP receptor, BMPRII, in the tips of neurites and binds to BMPRII. This interaction is required for BMP-dependent induction of the dendritic arbor in cortical neurons. Furthermore, we demonstrate that the physical interaction of LIMK1 with BMPRII synergizes with the Rho GTPase, Cdc42, to activate LIMK1 catalytic activity. These studies thus define a Smad-independent pathway that directly links the BMP receptor to regulation of actin dynamics and provides insights into how extracellular signals modulate LIMK1 activity to permit fine spatial control over cytoskeletal remodelling during dendritogenesis.
Lee-Hoeflich
Si Tuen
ST
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Causing
Carrie G
CG
Podkowa
Monika
M
Zhao
Xin
X
Wrana
Jeffrey L
JL
Attisano
Liliana
L
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D055419:Bone Morphogenetic Protein 7; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D054461:Lim Kinases; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II; D020764:cdc42 GTP-Binding Protein