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First published online October 24, 2007
doi: 10.1242/10.1242/jcs.011130

Journal of Cell Science 120, 3820-3829 (2007)
Published by The Company of Biologists 2007
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Research Article

SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility

Stella Tournaviti1,*, Sebastian Hannemann2,*, Stefan Terjung3, Thomas M. Kitzing4, Carolin Stegmayer1, Julia Ritzerfeld1, Paul Walther5, Robert Grosse4, Walter Nickel1,{ddagger} and Oliver T. Fackler2,{ddagger}

1 Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
2 Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
3 Advanced Light Microscopy Facility, EMBL, Meyerhofstr. 1, Heidelberg, Germany
4 Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
5 Electron Microscopy Facility, University Ulm, 89069 Ulm, Germany

{ddagger} Authors for correspondence (e-mails: walter.nickel{at}bzh.uni-heidelberg.de; oliver_fackler{at}med.uni-heidelberg.de)

Accepted 22 August 2007

SH4 domains provide bipartite membrane-targeting signals for oncogenic Src family kinases. Here we report the induction of non-apoptotic plasma membrane (PM) blebbing as a novel and conserved activity of SH4 domains derived from the prototypic Src kinases Src, Fyn, Yes and Lck as well as the HASPB protein of Leishmania parasites. SH4-domain-induced blebbing is highly dynamic, with bleb formation and collapse displaying distinct kinetics. These reorganizations of the PM are controlled by Rho but not Rac or Cdc42 GTPase signalling pathways. SH4-induced membrane blebbing requires the membrane association of the SH4 domain, is regulated by the activities of Rock kinase and myosin II ATPase, and depends on the integrity of F-actin as well as microtubules. Endogenous Src kinase activity is crucial for PM blebbing in SH4-domain-expressing cells, active Src and Rock kinases are enriched in SH4-domain-induced PM blebs, and PM blebbing correlates with enhanced cell invasion in 3D matrices. These results establish a novel link between SH4 domains, Src activity and Rho signalling, and implicate SH4-domain-mediated PM dynamization as a mechanism that influences invasiveness of cells transformed by SH4-domain-containing oncoproteins.

Key words: SH4 domain, Membrane blebbing, Cell invasion, Src, Rocka




This article has been cited by other articles:


Home page
 J. Cell Biol.Home page
O. T. Fackler and R. Grosse
Cell motility through plasma membrane blebbing
J. Cell Biol., June 16, 2008; 181(6): 879 - 884.
[Abstract] [Full Text] [PDF]


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