This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grove, M.
Right arrow Articles by Pendergast, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grove, M.
Right arrow Articles by Pendergast, A. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2004, p. 10905-10922, Vol. 24, No. 24
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.24.10905-10922.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Abi2-Deficient Mice Exhibit Defective Cell Migration, Aberrant Dendritic Spine Morphogenesis, and Deficits in Learning and Memory

Matthew Grove,1 Galina Demyanenko,2 Asier Echarri,1 Patricia A. Zipfel,1 Marisol E. Quiroz,1 Ramona M. Rodriguiz,3 Martin Playford,1 Shelby A. Martensen,1 Matthew R. Robinson,1 William C. Wetsel,3 Patricia F. Maness,2 and Ann Marie Pendergast1*

Department of Pharmacology and Cancer Biology,1 Departments of Psychiatry, Medicine (Endocrinology), and Cell Biology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham,2 Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina3

Received 4 June 2004/ Returned for modification 14 July 2004/ Accepted 14 September 2004

The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression. In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. These phenotypes were consistent with the localization of Abi2 at adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions.

* Corresponding author. Mailing address: Duke University Medical Center, Department of Pharmacology and Cancer Biology, Box 3813, Durham, NC 27710. Phone: (919) 681-8086. Fax: (919) 681-7148. E-mail: pende014{at}mc.duke.edu.

Molecular and Cellular Biology, December 2004, p. 10905-10922, Vol. 24, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.24.10905-10922.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bradley, W. D., Koleske, A. J. (2009). Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts. J. Cell Sci. 122: 3441-3454 [Abstract] [Full Text]  
  • Nowak, R. B., Fischer, R. S., Zoltoski, R. K., Kuszak, J. R., Fowler, V. M. (2009). Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens. JCB 186: 915-928 [Abstract] [Full Text]  
  • Lin, T.-Y., Huang, C.-H., Kao, H.-H., Liou, G.-G., Yeh, S.-R., Cheng, C.-M., Chen, M.-H., Pan, R.-L., Juang, J.-L. (2009). Abi plays an opposing role to Abl in Drosophila axonogenesis and synaptogenesis. Development 136: 3099-3107 [Abstract] [Full Text]  
  • Hotulainen, P., Llano, O., Smirnov, S., Tanhuanpaa, K., Faix, J., Rivera, C., Lappalainen, P. (2009). Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. JCB 185: 323-339 [Abstract] [Full Text]  
  • Ryu, J. R., Echarri, A., Li, R., Pendergast, A. M. (2009). Regulation of Cell-Cell Adhesion by Abi/Diaphanous Complexes. Mol. Cell. Biol. 29: 1735-1748 [Abstract] [Full Text]  
  • Rao, P. V., Maddala, R. (2009). Abundant Expression of Ponsin, a Focal Adhesion Protein, in Lens and Downregulation of Its Expression by Impaired Cytoskeletal Signaling. IOVS 50: 1769-1777 [Abstract] [Full Text]  
  • Schmidt, K. L., Marcus-Gueret, N., Adeleye, A., Webber, J., Baillie, D., Stringham, E. G. (2009). The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1. Development 136: 563-574 [Abstract] [Full Text]  
  • Ramos, R. L., Smith, P. T., DeCola, C., Tam, D., Corzo, O., Brumberg, J. C. (2008). Cytoarchitecture and Transcriptional Profiles of Neocortical Malformations in Inbred Mice. Cereb Cortex 18: 2614-2628 [Abstract] [Full Text]  
  • Zandy, N. L., Playford, M., Pendergast, A. M. (2007). Abl tyrosine kinases regulate cell cell adhesion through Rho GTPases. Proc. Natl. Acad. Sci. USA 104: 17686-17691 [Abstract] [Full Text]  
  • Fukui, M., Rodriguiz, R. M., Zhou, J., Jiang, S. X., Phillips, L. E., Caron, M. G., Wetsel, W. C. (2007). Vmat2 Heterozygous Mutant Mice Display a Depressive-Like Phenotype. J. Neurosci. 27: 10520-10529 [Abstract] [Full Text]  
  • Soderling, S. H., Guire, E. S., Kaech, S., White, J., Zhang, F., Schutz, K., Langeberg, L. K., Banker, G., Raber, J., Scott, J. D. (2007). A WAVE-1 and WRP Signaling Complex Regulates Spine Density, Synaptic Plasticity, and Memory. J. Neurosci. 27: 355-365 [Abstract] [Full Text]  
  • Rakeman, A. S., Anderson, K. V. (2006). Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching. Development 133: 3075-3083 [Abstract] [Full Text]  
  • Calabrese, B., Wilson, M. S., Halpain, S. (2006). Development and Regulation of Dendritic Spine Synapses. Physiology 21: 38-47 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»