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New mechanism to control the actin cytoskeleton of the mammalian cell

last modified Dec 12, 2013 04:09 PM

8 August 2011

Phospholipid membrane-coated beads
Figure: Phospholipid membrane-coated beads, incubated in a brain cell extract, assemble actin "comet tails" (red) which propel the beads through the extract.
Animal and plant cells contain a dynamic network of actin filaments, which are assembled and disassembled to drive fundamental processes such as cell migration, phagocytosis, synapse plasticity and tissue repair, and also pathologies like tumour and pathogen invasion. Prof Vassilis Koronakis and colleagues study how pathogenic bacteria exploit this actin cytoskeleton to establish infection. The newest findings from the Koronakis lab emphasise how such research is not only key to understanding and countering bacterial disease, but also in uncovering new aspects of mammalian cell biology.

Animal and plant cells contain a dynamic network of actin filaments, which are assembled and disassembled to drive fundamental processes such as cell migration, phagocytosis, synapse plasticity and tissue repair, and also pathologies like tumour and pathogen invasion. Prof Vassilis Koronakis and colleagues study how pathogenic bacteria exploit this actin cytoskeleton to establish infection. The newest findings from the Koronakis lab emphasise how such research is not only key to understanding and countering bacterial disease, but also in uncovering new aspects of mammalian cell biology.

Recently Prof Koronakis successfully developed a new technique for studying the actin cytoskeleton. He introduced silica beads coated with phospholipid membrane bilayers into a mammalian brain cell extract, such that the beads recruit the cellular machinery that triggers assembly of actin filaments, and generates actin ‘comet tails’ that propel the beads energetically through the extract (see Figure). Koronakis and his colleagues Drs Peter Hume and Daniel Humphreys have used this innovative assay to study the pathways controlling actin assembly, focusing in particular on the cellular WAVE complex, a critical regulator of actin filament production. They have discovered that membrane recruitment and activation of the WAVE complex requires the cooperative action of two mammalian GTPases, Arf and Rac. Arf directly recruits WAVE to membranes and is required to activate WAVE, while Rac is dispensable for recruitment, but necessary for Arf-dependent actin assembly. This previously unknown dual control and synergy represents a new level of complexity in the mechanisms the cell uses to control the actin cytoskeleton, and has profound implications for understanding normal and pathogenic actin-dependent cellular processes.

Current work by the group, together with its graduate students Anthony Davidson and Qi Hui Sam, is delving further into this key mammalian phenomenon, and is showing that Salmonella, the infamous intestinal pathogen that infects humans and animals, exploits this newly discovered mechanism in taking control of the cytoskeleton to invade host cells.


For more information contact Professor Vassilis Koronakis (vk103@cam.ac.uk). This work was funded by the Wellcome Trust and the Newton Trust

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WAVE regulatory complex activation by cooperating GTPases Arf and Rac1.
Koronakis V, Hume PJ, Humphreys D, Liu T, Hørning O, Jensen ON, McGhie EJ.
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14449-54.

The Salmonella effector SptP dephosphorylates host AAA+ ATPase VCP to promote development of its intracellular replicative niche.
Humphreys D, Hume, PJ and Koronakis, V
Cell Host Microbe, 2009; 5:225-33.