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Molecular and Cellular Biology, March 2009, p. 1506-1514, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.00857-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tropomyosin Isoform Expression Regulates the Transition of Adhesions To Determine Cell Speed and Direction{triangledown} ,{dagger}

Cuc T. T. Bach,1,2 Sarah Creed,1,2 Jessie Zhong,1 Maha Mahmassani,1 Galina Schevzov,1,2 Justine Stehn,1,2 Lauren N. Cowell,1,2 Perttu Naumanen,3 Pekka Lappalainen,3 Peter W. Gunning,1,2 and Geraldine M. O'Neill1,2*

Oncology Research Unit, Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia,1 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales 2006, Australia,2 Institute of Biotechnology, University of Helsinki, Helsinki FI-00014, Finland3

Received 29 May 2008/ Returned for modification 5 September 2008/ Accepted 25 December 2008

The balance of transition between distinct adhesion types contributes to the regulation of mesenchymal cell migration, and the characteristic association of adhesions with actin filaments led us to question the role of actin filament-associating proteins in the transition between adhesive states. Tropomyosin isoform association with actin filaments imparts distinct filament structures, and we have thus investigated the role for tropomyosins in determining the formation of distinct adhesion structures. Using combinations of overexpression, knockdown, and knockout approaches, we establish that Tm5NM1 preferentially stabilizes focal adhesions and drives the transition to fibrillar adhesions via stabilization of actin filaments. Moreover, our data suggest that the expression of Tm5NM1 is a critical determinant of paxillin phosphorylation, a signaling event that is necessary for focal adhesion disassembly. Thus, we propose that Tm5NM1 can regulate the feedback loop between focal adhesion disassembly and focal complex formation at the leading edge that is required for productive and directed cell movement.


* Corresponding author. Mailing address: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. Phone: 61 2 98453116. Fax: 61 2 98453078. E-mail: geraldio{at}chw.edu.au

{triangledown} Published ahead of print on 5 January 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, March 2009, p. 1506-1514, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.00857-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.