![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 7, 3433-3449, July 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Instituto Investigacion Medica Mercedes y Martin Ferreya-CONICET-Consejo Nacional de Investigaciones Científicas y Técnicas, 5000 Cordoba, Argentina;
Division of Biochemistry, Osaka University Medical School, Osaka 565-0871, Japan;
Centro Investigacion Quimica Biologica Cordoba-CONICET-Consejo Nacional de Investigaciones Científicas y Técnicas, 5000 Cordoba, Argentina; and
|| Institute for Neuroscience and Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611
Submitted May 23, 2003;
Revised March 30, 2004;
Accepted April 9, 2004
Monitoring Editor: Anne Ridley
In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips. Overexpression of wild-type LIMK1 suppresses the formation of trans-Golgi derived tubules, and prevents cytochalasin D-induced Golgi fragmentation, whereas that of a kinase-defective mutant has the opposite effect. Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, while inhibiting the Golgi export of synaptophysin-containing vesicles. These effects were dependent on the Golgi localization of LIMK1, paralleled by an increase in cofilin phosphorylation and phalloidin staining in the region of the Golgi apparatus, and prevented by coexpression of constitutive active cofilin. The long-term overexpression of LIMK1 produces growth cone collapse and axon retraction, an effect that is dependent on its growth cone localization. Together, our results suggest an important role for LIMK1 in axon formation that is related with its ability to regulate Golgi dynamics, membrane traffic, and actin cytoskeletal organization.
Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.
These authors contributed equally to this study.
¶ Corresponding author. E-mail address: acaceres{at}immf.uncor.edu.
This article has been cited by other articles:
|
|
 |
|
  K. Abu-Elneel, T. Ochiishi, M. Medina, M. Remedi, L. Gastaldi, A. Caceres, and K. S. Kosik A {delta}-Catenin Signaling Pathway Leading to Dendritic Protrusions J. Biol. Chem., November 21, 2008; 283(47): 32781 - 32791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bisbal, C. Conde, M. Donoso, F. Bollati, J. Sesma, S. Quiroga, A. Diaz Anel, V. Malhotra, M. P. Marzolo, and A. Caceres Protein Kinase D Regulates Trafficking of Dendritic Membrane Proteins in Developing Neurons J. Neurosci., September 10, 2008; 28(37): 9297 - 9308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-M. Yin, Y.-H. Huang, Y.-B. Zhu, and Y. Wang Both the Establishment and Maintenance of Neuronal Polarity Require the Activity of Protein Kinase D in the Golgi Apparatus J. Neurosci., August 27, 2008; 28(35): 8832 - 8843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sanchez, L. Gastaldi, M. Remedi, A. Caceres, and C. Landa Rotenone-Induced Toxicity is Mediated by Rho-GTPases in Hippocampal Neurons Toxicol. Sci., August 1, 2008; 104(2): 352 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Endo, K. Ohashi, and K. Mizuno LIM Kinase and Slingshot Are Critical for Neurite Extension J. Biol. Chem., May 4, 2007; 282(18): 13692 - 13702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. Bernstein, H. Chen, J. A. Boyle, and J. R. Bamburg Formation of actin-ADF/cofilin rods transiently retards decline of mitochondrial potential and ATP in stressed neurons Am J Physiol Cell Physiol, November 1, 2006; 291(5): C828 - C839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Heredia, P. Helguera, S. de Olmos, G. Kedikian, F. Sola Vigo, F. LaFerla, M. Staufenbiel, J. de Olmos, J. Busciglio, A. Caceres, et al. Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. J. Neurosci., June 14, 2006; 26(24): 6533 - 6542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Acevedo, N. Moussi, R. Li, P. Soo, and O. Bernard LIM Kinase 2 Is Widely Expressed in All Tissues J. Histochem. Cytochem., May 1, 2006; 54(5): 487 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gardet, M. Breton, P. Fontanges, G. Trugnan, and S. Chwetzoff Rotavirus Spike Protein VP4 Binds to and Remodels Actin Bundles of the Epithelial Brush Border into Actin Bodies. J. Virol., April 1, 2006; 80(8): 3947 - 3956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Tursun, A. Schluter, M. A. Peters, B. Viehweger, H. P. Ostendorff, J. Soosairajah, A. Drung, M. Bossenz, S. A. Johnsen, M. Schweizer, et al. The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones Genes & Dev., October 1, 2005; 19(19): 2307 - 2319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. D. Anel and V. Malhotra PKC{eta} is required for {beta}1{gamma}2/{beta}3{gamma}2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus J. Cell Biol., April 11, 2005; 169(1): 83 - 91. [Abstract] [Full Text] [PDF]
|
|
