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IN THIS ISSUE |
The tubulin superfamily (p. 2723) Commentary
The `multi-tubulin hypothesis' formulated a quarter of a century agopostulated that eukaryotes use different forms of the protein tubulin toconstruct a wide variety of microtubule-based structures. Since then, workersin the field have identified a host of distinct 
ß-tubulin isotypesand post-translational modifications that can influence microtubule structureand function. Keith Gull and co-workers review our understanding of the rolesof these different tubulins and re-examine the multi-tubulin hypothesis in thelight of recent work. Studies of the C. elegans ß-tubulinisotype MEC-7, for example, indicate that it endows the axons of touchreceptor neurones with a distinct, 15-protofilament organization. Additionalevidence for the specialization of different forms of tubulin arises from therecent demonstration that microtubules in the basal bodies ofDrosophila sperm contain only ß1-tubulin whereas the spermflagellar axoneme contains only ß2-tubulin. Similarly, 
-tubulinappears to have a specific role in nucleation of microtubules. The tubulinsuperfamily is now known to extend to at least seven members. Gull andco-workers propose that specialization extends to the recently identified
, 
, 
and 
tubulins, which they suggest might benecessary for construction or inheritance of complex centrioles or basalbodies.
Cell migration and Rho GTPases (p. 2713) Signal Transduction and Cellular Organization
Cell migration is essential for normal development and responses toinfection or tissue damage. The dynamic changes to the cytoskeleton and celladhesion required are coordinated by signalling pathways that respond toexternal cues. A wide variety of signalling molecules are involved, butRho-family small GTPases (e.g. Rac, Rho and Cdc42) appear to be key players.Anne Ridley discusses research that has shed light on the roles of Rho GTPasesin cell migration, focusing on cytoskeletal rearrangements and cell-substrateadhesion. The Rho-family GTPase Rac, for example, has been shown to have animportant role. Active Rac is localized at the front of migrating cells.Furthermore, it can induce actin polymerization during lamellipodium formationboth by stimulating the Arp2/3 complex (via IRSp53 and WAVE) and by promotinguncapping of actin filaments (through PIP-5-kinase-dependent generation ofPtdIns(4,5)P2). Rho GTPases also appear to regulate thedynamics of other cytoskeletal filaments (microtubules and intermediatefilaments) during migration, acting through Rho effectors such as the PAK andROCK kinases.
Theileria annulata parasite AT-hook proteins (p. 2747)
Theileria annulata is a tick-borne apicomplexan parasite thatinfects bovine white blood cells, causing them to proliferate uncontrollablyand infiltrate all major organ systems. The parasite appears to induceimmortalization of infected host cells by stimulating changes in theexpression of genes that control cell division or apoptosis. Quite how it doesthis has remained obscure. David Swan and co-workers now describe a group ofparasite DNA-binding proteins that could be responsible for parasite-inducedchanges in host gene expression. They show that T. annulata encodesthree closely related proteins - TashAT1, TashAT2 and TashAT3 - that containAT-hook DNA-binding motifs. The authors demonstrate that all three proteinsare able to bind to AT-rich DNA. Furthermore, they show that the TashATproteins are present in parasite-infected cells and appear to be transportedto the host cell nucleus. Since AT-hook proteins play important roles ineukaryotic gene expression and cell proliferation, Swan and co-workers proposethat TashAT proteins have a similar function in Theileria-infectedcells.
Adipogenesis regulation by the arylhydrocarbon receptor (p. 2809)
The arylhydrocarbon receptor (AhR) is a ligand-activated bHLH transcriptionfactor that plays an important role in xenobiotic metabolism. It mediates theeffects of toxins such as tetrachlorodibenzo-p-dioxin (TCDD) butmight also function in embryonic development and homeostasis. Shigeki Shimbaand co-workers provide evidence that AhR negatively regulates adiposedifferentiation. They demonstrate that antisense AhR induces morphologicaldifferentiation of 3T3-L1 cells to form adipocytes and promotes expression ofseveral adipocyte-specific genes, whereas overexpression of AhR suppressesdifferentiation and induction of these genes. Interestingly, expression ofperoxisome proliferator activator receptor 2 (PPAR2), which hasa pivotal role in adipogenesis, is unaffected by overexpression of AhR, andactivation of PPAR2 can restore the ability of AhR-expressing cells todifferentiate. The authors show that the effects of AhR are mediated by MAPkinase and that AhR inhibits the pRB phosphorylation and p107 downregulationcharacteristic of adipogenesis. Since downregulation of p107 is essential forPPAR2 activation, Shimba and co-workers suggest that a key target ofAhR is the PPAR2 activation pathway.
Mitochondrial swelling and cytochrome C release (p. 2855)
A critical role of mitochondria in apoptosis is the release of cytochromeC. Once in the cytoplasm, cytochrome C binds to Apaf1 and activates thecaspase cascades that cause cell death. Many investigators believe that therelease of cytochrome C is due to swelling and consequent rupture ofmitochondria in response to apoptotic stimuli. Donald Chang and co-workers,however, now show that this is not the case. They have monitored changes inmitochondrial morphology and the dynamics of GFP-tagged cytochrome C duringapoptosis induced by a variety of stimuli in intact living cells. The authorsfind that swelling of mitochondria indeed occurs but does not necessarilycause a rupture in the outer membrane. Furthermore, they demonstrate thatcytochrome C is released 
10 min before mitochondria swell. Changand co-workers propose that cytochrome C release is a cause rather than aconsequence of mitochondrial swelling and that the latter could be due toreactive oxygen species generated after cytochrome C is released.
Sticky Wicket - 24 hours in the day (p. 2709)
Most professions are based around a 9-5 working day. But scientists aregenerally expected to work longer hours. Caveman ponders why this is - it can't be the pay!
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