|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
In this issue |
Tubby-like proteins (p. 9) Commentary
The tubby-like proteins (TULPs) are a small protein family that has representatives in plants and animals. Mutations in the founder member - tubby - are associated with obesity and specific neurosensory defects in mice; however, the strong evolutionary conservation of these proteins and the lethality of the Tulp3–/– knockout suggests that TULPs have a fundamental cellular function. Jürgen Naggert and co-workers review progress in our understanding of the roles of this recently identified family. Genetic analyses indicate that the primary site of action of TULPs is neuronal cells, in which the absence of TULPs leads to apoptosis. Moreover, they show that the functionally important domain is the highly conserved C-terminal domain - a unique 12-stranded ß-barrel with a hydrophobic core. Other work indicates that signalling by neuronal G-protein-coupled receptors such as 5HT2c and D1 receptors causes translocation of TULPs from the plasma membrane to the nucleus, where they could regulate gene expression. They might also regulate vesicle trafficking, having been implicated in control of opsin transport in photoreceptor cells.
Kinesin mechanics (p. 15) Commentary
An important goal of research into cytoskeletal motors is to define the structural changes that occur as the motor hydrolyses ATP and binds to its filament. In the case of myosin, distinct structural states have been defined (although critical structures are still missing). Kinesin states, by contrast, have proven more elusive. Recent crystal structures of Kar3 mutants and of KIF1A bound to an ATP analogue shed new light on the kinesin mechanism. The structures differ from previous kinesin-ADP crystal structures in two important respects: (1) the switch I region near the nucleotide-binding cleft is no longer a short helix but instead a pseudo-ß-hairpin or completely disordered; and (2) the switch II or ‘relay’ helix is reoriented and repositioned. Jon Kull and Sharyn Endow discuss the implications of these differences in terms of ATP hydrolysis and microtubule binding. They propose that one important structural transition is a dramatic alteration in the conformation of the switch I region during nucleotide hydrolysis, which interferes with coordination of the associated Mg2+ ion and thereby causes ADP release.
Linking the DNA damage and mitotic checkpoints (p. 71)
Kinetochores (the protein assemblies that link centromeres to spindle microtubules) play an important role at the mitotic checkpoint: they monitor attachment of spindle microtubules, delaying entry into anaphase until they have sensed the tension generated by bipolar attachment. Several proteins have been implicated in this process, including MAD1/2, BUBR1 and CENP-E. Yasuhisa Adachi and co-workers now add another to this list: the BRCT-domain protein 53BP1. What is interesting about 53BP1 is that it is also a component of another checkpoint pathway: the DNA damage response. The authors demonstrate that 53BP1 associates with kinetochores during prophase but leaves by mid-anaphase. In common with other mitotic checkpoint proteins, it is more concentrated on unaligned chromosomes. Moreover, it is more heavily hyperphosphorylated after spindle disruption and might therefore, like BUBR1, be phosphorylated when the mitotic checkpoint is activated. This involvement of a known component of the DNA damage response in the mitotic checkpoint indicates that checkpoints previously thought to be unrelated could share common components.
Microtubule dynamics (p. 3 + poster) Cell Science at a Glance
Microtubules have fundamental roles in a variety of cellular processes, including cell movement, vesicle transport and chromosome segregation. Many of these processes require dynamic, but controlled, reorganization of the microtubule cytoskeleton. Cells have therefore developed numerous mechanisms for regulating the synthesis, length and stability of microtubules. Rebecca Heald and Eva Nogales survey our understanding of microtubule dynamics, illustrating the intrinsic instability of microtubules as well as the cellular factors that further modify the dynamics of these cytoskeletal polymers.
Extracellular regulation of cyclin A degradation (p. 123)
Dally is a Drosophila membrane proteoglycan involved in tissue-specific responses to Wingless and Decapentaplegic signalling. dally mutants exhibit delayed cell cycle progression in specific regions of the developing eye and consequently abnormal morphogenesis. The protein is thought to promote organization of signalling complexes at the cell surface, but how it regulates cell cycle progression is unclear. Scott Selleck and co-workers have used genetics to address this question. They show that mutations that reduce cyclin A levels (but not those affecting cyclin B levels) suppress many of the developmental defects observed in dally flies. In addition, they demonstrate that, in dally mutants, cyclin A is present in affected cells at metaphase - a stage at which the cyclin has normally been degraded. Selleck and co-workers conclude that Dally regulates cell cycle progression in specific cell populations by controlling the degradation of cyclin A, providing one of the first indications that extracellular cues can regulate this aspect of mitotic progression.
Sticky Wicket - meeting locations (p. 1)
Does the location of a meeting matter? And is the quality of the accommodation provided inversely proportional to the quality of the science? Caveman ponders these questions while deciding whether to accept a recent invitation to attend a meeting in Europe.
Related articles in JCS:
This article has been cited by other articles:
|
|
 |
|
  A. Alter, M. Duddy, S. Hebert, K. Biernacki, A. Prat, J. P. Antel, V. W. Yong, R. K. Nuttall, C. J. Pennington, D. R. Edwards, et al. Determinants of Human B Cell Migration Across Brain Endothelial Cells J. Immunol., May 1, 2003; 170(9): 4497 - 4505. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||
