BAF goes nuclear

Two channels, one program he biophysical and structural characteristics of chloride ion channels have been studied extensively, but little is known about the molecular regulation and signaling pathways associated with these highly conserved proteins. Rutledge et al. (page 435) analyzed the activation of the CLH-3 chloride ion channel in C. elegans during meioitic cell cycle progression and in response to oocyte swelling. The work demonstrates the utility of the worm system in studying these channels, and suggests that CLH-3 and its putative mammalian orthologue, ClC-2, respond to similar regulatory inputs to carry out similar physiological functions. The authors found that during oocyte maturation, or in response to oocyte swelling, CLH-3 is activated by serine/ threonine dephosphorylation. RNAi inhibition demonstrates that the dephosphorylation is mediated by CeGLC-7 ␣ and CeGLC-7 ␤ , phosphatases that help to regulate meiotic and mitotic cell cycles in worms. Rat ClC-2 heterologously expressed in mammalian cells is also activated by serine/ threonine dephosphorylation, suggesting that the two channels share a common regulatory mechanism, despite their wide evolutionary separation. Rutledge et al. suggest that both channels may depolarize membranes to transduce signals between cell types, such as worm oocytes and the surrounding contractile sheath cells, that are coupled by gap junctions. ᭿ T A phosphatase inhibitor (CA) prevents meiotic maturation–induced current. BAF goes nuclear arrier-to-autointegration factor (BAF) was first described as a cellular activity that prevents retroviral DNA from undergoing suicidal autointegration, but its function in uninfected cells remained obscure. Segura-Totten et al. (page 475) have now performed a detailed biochemical characterization of BAF. The work defines critical functional motifs of this DNA-bridging protein, and suggests that BAF is essential for chromatin decondensation and nuclear envelope assembly and growth. Previous work had shown that BAF binds to DNA and to proteins containing a LEM domain, a structure that defines a family of nuclear membrane proteins. B A new path for endostatin he ability of endostatin to inhibit angiogenesis has produced sensational headlines, but efforts to understand how this collagen fragment actually works have drawn considerably less fanfare. On page 529, Hanai et al. now demonstrate that endostatin acts through a novel pathway to inhibit Wnt signaling, suggesting that the effects of endostatin on tumors may be more complex than previously thought. Using Xenopus embryonic development as a model system, the authors found that high concentrations of endostatin produced developmental abnormalities characteristic of Wnt signaling defects, a notion …