BSCB Newsletter, Summer 2004

BSCB Spring Meeting 2004

Spring meeting introduction
Cytoskeleton and Cell Polarity
Protein Modification and Degradation
Biological imaging
Mechanosensation and organogenesis
Nuclear lamins in cell biology and disease
Dynamics of cell matrix interactions
Dynamics of cell-cell adhesion
Cellular Microenvironment
Hooke Medal and plenary lectures
Lord Sainsbury’s speech
Lunchtime discussions

Cytoskeleton and Cell Polarity

Thursday morning began early with an exciting, wide-ranging session on Cytoskeleton and Cell Polarity which included studies on plants, yeast and mammalian cells. Laura Machesky (University of Birmingham) began this session by discussing the molecular mechanisms involved in cellular dynamics. In particular, how cell signalling mediated through the WASP-family of proteins activates the Arp2/3 complex, which then leads to the assembly and disassembly of actin filaments. She presented data on the IRSp53/MIM family of proteins, adaptor proteins that link the small GTPase, Rac1, to the WASP-family protein, WAVE2. The IRSp53/MIM family have an actin-bundling function and bind actin through a specific domain, termed IMD (IRSp53/MIM homology domain).  When overexpressed in cells, IRSp53 or MIM induce filopodia and other membrane protrusions and when the IMD is deleted the protein loses its membrane localisation.

Kathryn Ayscough (University of Sheffield) then presented her lab’s work on the newly recognised role of the actin cytoskeleton in ageing and apoptosis in Saccharomyces cerevisiae.  Yeast mutants with reduced actin dynamics showed loss of mitochondrial function and contained greater levels of reactive oxygen species than wild type cells and as a consequence died prematurely. Significantly, the number of reactive oxygen species decreased in mutant cells with increased actin dynamics and the cells had greater viability and replicative capacity.

Patrick Hussey (University of Durham) described actin binding proteins in plants and in particular the roles of ADF and AIP1 in the signalling pathways controlling actin dynamics in Arabidopsis. The importance of AIP1 in plant development was shown using ethanol-induced AIP1 RNAi expression. Loss of function resulted in stabilised actin bundles and a reduction in cell growth, perhaps caused by a decrease in F-actin turnover and the promotion of actin bundling.  He also discussed the possible parallels between the control of the ARP2/3 complex in plants and other organisms and suggested that the differences between systems are often more interesting than the similarities.

Sandrine Etienne-Manneville (Institut Curie, Paris, France) described the importance of microtubule organisation in polarised migrating cells.  Primary rat astrocytes were studied using a combination of scratch-induced migration assays and Total Internal Reflection Fluorescent Microscopy (TIRF), a technique that allows detailed examination of proteins close to the basal membrane. Her lab has elucidated a pathway downstream of Cdc42 that leads to microtubule end capture at a site containing APC.  A complex of APC and EB1 is required for microtubule capture and this is essential for centrosome reorientation and cell polarisation.

Roy Quinlan (Durham University) discussed the importance of the lens-specific intermediate filament protein,CP49. Mutations in this protein cause cataracts in humans but, unexpectedly, CP49 knockout in the mouse didn’t induce cataracts but did lead to increased light scatter in the lens.  This was a result of the dramatic reorganisation of the plasma membrane in lens fibre cells and a depolarisation of organised membrane compartments with a concurrent loss of the optical properties of the lens.  This model can be used to study the relationship between cell compartmentalisation, polarity and the intermediate filament cytoskeleton.

Finally, Michel Bornens (Institut Curie, Paris, France) presented an interesting technique for the study of the relationship between cell adhesion patterns and the control of the cell division axis in mammalian cells.  He described the use of microcontact printing coupled with automated image analysis to look at the distribution of retraction fibres in dividing cells and how it affects the orientation of the mitotic spindle axis.  He also showed that post-mitotic cell spreading correlates over time with all the former ruffling contacts of the mother cell.