On the cover
The gut epithelia of mice expressing the fluorescently labeled tight junction proteins occludin (green) and ZO-1 (red). Marchiando et al. reveal that the cytokine TNF disrupts the barrier function of tight junctions by stimulating the caveolin-1–dependent endocytosis of occludin.
See page 111.
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Philip Siekevitz, an Emeritus Professor at the Rockefeller University who made pioneering contributions to the development of modern cell biology, passed away on December 5th, 2009. He was a creative and enthusiastic scientist, as well as a great experimentalist who throughout his lifetime transmitted the joy of practicing science and the happiness that comes with the acquisition of new knowledge. He was a man of great integrity, with a thoroughly engaging personality and a humility not often found in people of his talent.
In This Issue
People & Ideas
PDGF enhances podosome formation and cell migration by regulating expression of the microRNAs miR-143 and -145, which target PDGF-R, PKC-ε, and fascin.
Two domains of centrosomal protein CDK5RAP2, CNN1 and CNN2, link centrosomes to mitotic spindle poles. CNN1 lacking centrosomes are unable to recruit pericentriolar matrix components that mediate attachment to spindle poles.
Spindle pole body components Spc29 and Cdc31 are identified as targets of Mps1 kinase, which, when phosphorylated, regulate protein–protein interactions in the spindle pole body.
A dual function for chaperones SSB–RAC and the NAC nascent polypeptide–associated complex on ribosomes
In addition to assisting with protein folding, SSB and NAC also regulate ribosome biogenesis (see also companion paper from Albanèse et al. in this issue).
Ribosome-anchored proteins Jjj1 and Zuo1 function together with Hsp70 to mediate ribosome biogenesis (see also the companion paper from Koplin et al. in this issue).
AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis
Disturbances in cellular ion gradients by excitotoxicity promote apoptosis through activation of the Bcl-2 family member Bim.
In skeletal muscle fibers, tropomodulin 1 (Tmod1) can be compensated for, structurally but not functionally, by Tmod3 and -4.
Caveolin-1–dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo
Although tight junction morphology is not obviously affected by TNF, this proinflammatory cytokine promotes internalization of occludin, resulting in disrupted barrier function within the intestine.
The microRNA miR-137 represses expression of Ezh2, a histone methyltransferase, which in turn alters the epigenetic architecture of chromatin that is important for regulation of miR-137 levels.
Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila
How spectrin mutations caused Purkinje cell death becomes clearer following studies that examined the effect of expressing mutant SCA5 in the fly eye. Mutant spectrin causes deficits in synapse formation at the neuromuscular junction and disrupts vesicular trafficking.
Astrocyte differentiation and maintenance is promoted by BMP signaling, which induces REST/NRSF to repress neuronal genes.
IFT proteins are differentially localized in photoreceptor cilia, including within the inner segment, and some are shown to function in trafficking in nonciliated retinal neurons.