News & Views in 2005

Talin is a core component of the integrin adhesion complex. It is now shown that talin also regulates transcription, an activity that is apparently independent of its interaction with integrins. Talin represses the expression of Drosophila melanogaster DE-cadherin through an unknown molecular mechanism.

Conditional knockout of the KAP3 subunit from the kinesin motor KIF3 alters tissue patterning and causes abnormal proliferation of neural progenitor cells in the mouse brain. Impaired transport of N-cadherin to the surface of these cells may be one explanation for how such defects arise.

Highly localized Ca²⁺ signals called Ca²⁺ sparks have been widely reported in all mammalian muscle types except adult skeletal muscle. We now learn that these mysteriously absent sparks can be seen during stress or disease, raising the question of how these signals become unmasked in these conditions.

By what molecular mechanisms do microtubules regulate the spatial distribution of actin assembly in cells? In fission yeast, a novel SH3-domain-containing protein, Tea4p, acts to bridge the microtubule plus-end-binding protein Tea1p with the actin-nucleating formin protein For3p.

Vesicle formation at the trans-Golgi network may be mechanistically more similar to endocytic vesicle formation at the plasma membrane than previously thought. Both processes share common components including the dynamin-binding protein cortactin.

The HIV type 1 (HIV-1) life-cycle involves a number of cellular cofactors. Some are essential for HIV-1 replication and thus may serve as targets for therapeutic intervention. An emerging role for cellular DNA repair in HIV-1 infection suggests that inhibition of these repair functions may lead to suppression of viral replication.

Phosphorylation of synaptojanin 1 by the EphB2 receptor tyrosine kinase is a molecular switch. This phosphorylation prevents the interaction of synaptojanin 1 with endophilin and promotes endocytosis. Subsequent dephosphorylation initiates an interaction with endophilin, leading to clathrin uncoating and fusion with endosomes.

All members of the conserved family of structural maintenance of chromosomes (SMC) proteins are essential for cellular viability. The Smc1–Smc3 heterodimer is a constituent of cohesin and Smc2–Smc4 of condensin, which are both required for proper chromosome distribution at mitosis. Now, the third SMC heterodimer, Smc5–Smc6, which had previously been implicated only in DNA repair, also turns out to be crucial for chromosome segregation.

Monoubiquitination of the Fanconi anaemia protein FANCD2 is essential for its activity in DNA repair and tumour suppression. The recent identification of a specific de-ubiquitinating (DUB) enzyme for FANCD2 raises intriguing questions about how and why this tumour suppressor becomes deactivated.

Many biological processes require the movement of cells in response to guidance cues. Small GTPases and phosphoinositides are key mediators of the underlying cytoskeletal rearrangements, and a new study establishes that the localization and activation of the phosphoinositide phosphatase PTEN at the rear of chemotaxing neutrophils is mediated by the small GTPase RhoA.

How cells establish and maintain polarity during directed cell migration remains poorly understood. Nishiya et al. now describe an integrin signalling complex that includes paxillin and GIT1, which limits activation of Rac to the leading edge of a migrating cell.

Epidermal growth factor and nerve growth factor (NGF) lead to significantly different temporal patterns of extracellular-signal-regulated kinase activation, and differential regulation of Ras and Rap1 have been implicated in mediating this temporal specificity. Now Sasagawa et al. derive a computational model that incorporates the known signalling interactions and identifies key points of regulation that control these processes.

In this issue, two groups have examined the role of the Par proteins in the regulation of small G proteins, in two different models of cell polarity — mammalian epithelia and neuronal axon specification. They concurrently report the intriguing finding that the Par-3/Par-6/aPKC complex can regulate the activation of Rac by interaction with the guanine nucleotide exchanger, Tiam1/STEF. Furthermore, they also demonstrate a hitherto under-appreciated role for the Par-3/Par-6/aPKC complex in the regulation of the actin cytoskeleton.

Targeting substrates to the proteasome is generally thought to depend on long polyubiquitin chains that form on the substrate. Recent work has led to the provocative proposal that some substrates may be targeted to the proteasome through smaller chains that contain only four to six ubiquitin molecules.

Nuclear accumulation of the c-Abl tyrosine kinase is associated with a pro-apoptotic response after DNA damage, but the mechanism regulating c-Abl nuclear localization is unclear. DNA damage and other stress signals are now shown to induce phosphorylation of 14-3-3 proteins by the c-Jun amino-terminal kinase, disrupting a c-Abl/14-3-3 cytoplasmic complex, and liberating c-Abl for translocation to the nucleus.

Cancer cells have a raised cellular metabolism, including increased protein biosynthesis. Three new studies now show that the oncoprotein Myc, known to drive cell division, also enhances ribosomal RNA synthesis by RNA polymerase I in addition to controlling RNA polymerase II- and III-regulated gene transcription. This suggests that Myc promotes the generation of crucial components of a functional ribosome.

Actin polymerization is intimately associated with endocytosis in yeast and mammalian cells. Mechanisms of actin filament assembly in endocytosis are becoming better understood but less is known about how assembly is terminated. In yeast, phosphorylation of Arp2/3 complex activators provides one mechanism for downregulating endocytic actin assembly.