QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 26 February 2008
doi: 10.1242/jcs.013722

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.013722v1 121/6/854    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johansen, L. D. Articles by Kallunki, T. Search for Related Content PubMed PubMed Citation Articles by Johansen, L. D. Articles by Kallunki, T. Social Bookmarking                         What's this?

IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration

Lars Dan Johansen^1,*, Tiina Naumanen^1,*, Astrid Knudsen¹, Nina Westerlund², Irina Gromova³, Melissa Junttila², Christina Nielsen¹, Trine Bøttzauw¹, Aviva Tolkovsky⁴, Jukka Westermarck^2,5, Eleanor T. Coffey², Marja Jäättelä¹ and Tuula Kallunki^1,

¹ Apoptosis Department and Center for Genotoxic Stress, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
² Turku Centre for Biotechnology, Åbo Akademi and University of Turku, Turku, Finland
³ Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
⁴ Department of Biochemistry, University of Cambridge, Cambridge, UK
⁵ Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland

Author for correspondence (e-mail: tk{at}cancer.dk)

Accepted 6 December 2007

Loss-of-function mutations in the IKBKAP gene, which encodes IKAP (ELP1), cause familial dysautonomia (FD), with defective neuronal development and maintenance. Molecular mechanisms leading to FD are poorly understood. We demonstrate that various RNA-interference-based depletions of IKAP lead to defective adhesion and migration in several cell types, including rat primary neurons. The defects could be rescued by reintroduction of wild-type IKAP but not by FD-IKAP, a truncated form of IKAP constructed according to the mutation found in the majority of FD patients. Cytosolic IKAP co-purified with proteins involved in cell migration, including filamin A, which is also involved in neuronal migration. Immunostaining of IKAP and filamin A revealed a distinct co-localization of these two proteins in membrane ruffles. Depletion of IKAP resulted in a significant decrease in filamin A localization in membrane ruffles and defective actin cytoskeleton organization, which both could be rescued by the expression of wild-type IKAP but not by FD-IKAP. No downregulation in the protein levels of paxillin or beclin 1, which were recently described as specific transcriptional targets of IKAP, was detected. These results provide evidence for the role of the cytosolic interactions of IKAP in cell adhesion and migration, and support the notion that cell-motility deficiencies could contribute to FD.

Key words: Neuronal migration, Familial dysautonomia, ELP1, Paxillin, Beclin 1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Lipardi and B. M. Paterson Identification of an RNA-dependent RNA polymerase in Drosophila involved in RNAi and transposon suppression PNAS, September 15, 2009; 106(37): 15645 - 15650. [Abstract] [Full Text] [PDF]

				J. Gardiner, D. Barton, R. Overall, and J. Marc Neurotrophic Support and Oxidative Stress: Converging Effects in the Normal and Diseased Nervous System Neuroscientist, February 1, 2009; 15(1): 47 - 61. [Abstract] [PDF]