Volume 12 Issue 2, February 2010

Adipocytes and scar tissue form during skeletal muscle degeneration. Two new studies reveal that adipocytes and fibroblasts in skeletal muscle derive from a population of bipotent progenitors that reside within muscle, but are not derived from the muscle lineage. These progenitor cells also have a surprising role in stimulating the restoration of muscle mass during regeneration.

Recent studies have revealed a prominent role of mitochondrial dysfunction in the development of one of the most common neurodegenerative disorders, Parkinson's disease. The ubiquitin ligase Parkin and the protein kinase PINK1, whose mutations are associated with Parkinson's disease, function in a pathway that links ubiquitylation with selective autophagy of damaged mitochondria.

Separation of sister chromatids at anaphase in metazoan cells requires only the cleavage of the kleisin subunit of centromeric cohesin, but efficient poleward movement of separated sisters requires the associated loss in Cdk1 activity. Activation of the anaphase-promoting complex/cyclosome ensures these events are coordinated.

In budding yeast, many inducible genes translocate to the nuclear periphery when activated. Sequence motifs have now been identified in promoters, which target genes to the nuclear periphery and contribute to gene activation

The E3 ubiquitin ligase Parkin mediates the clearance of depolarized mitochondria through the autophagy pathway. PINK1 kinase activity is required for Parkin translocation to depolarized mitochondria where Parkin generates polyubiquitin chains on the voltage-dependent anion channel (VDAC1) to recruit the autophagic adaptor p62/SQSTM1.

Hedgehog signalling and activation of its downstream effectors Gli1/2 is deregulated in tumorigenesis. Hedgehog-induced HDAC1 is shown to activate Gli1/2 through its deacetylation. This effect is negatively regulated by the Cullin3/RENKCTD11 ubiquitin ligase, a Gli antagonist that is often lost in human medulloblastoma.

Ectopic adipocytes in skeletal muscle are observed in several disorders, but their origin is unclear. PDGFRα+ mesenchymal progenitors are identified as responsible for ectopic adipogenesis, which is inhibited by the presence of satellite cell-derived myofibres.

Following skeletal muscle damage, a population of resident fibro/adipogenic progenitors (FAP) initiates proliferation, resulting in the generation of ectopic white fat but not myofibres. FAPs enhance the differentiation of the myogenic progenitors involved in muscle regeneration.

The γ-tubulin ring complex (γ-TuRC) nucleates microtubules. The nuclear pore subcomplex Nup107-160 is found to interact and cooperate with γ-TuRC to nucleate microtubules at kinetochores, thereby promoting spindle assembly.

Mouse node cilia are posteriorly tilted to generate a leftward fluid flow and left/right asymmetry in the embryo, but how the tilt comes about was not known. The basal bodies of node cilia gradually shift from a central position towards the posterior side of node cells in a dishevelled and non-canonical Wnt signalling-dependent manner and follow a shift in Dvl localization to the posterior.

The ATM signalling mediator proteins 53BP1 and KAP-1 are required for heterochromatic double-strand break DNA repair. 53BP1 aids Mre11, NBS1 and ATM accumulation at heterochromatic breaks, leading to localized phosphorylation of KAP-1 by ATM.

Whether cohesion-independent forces hold chromosomes together in metaphase is a debated issue. Artificial cleavage of cohesin is sufficient to induce chromosome disjunction in Drosophila syncytical embryos but cdk1 inactivation is required for normal subsequent chromosome separation.

The role of Kaposi's sarcoma-associated herpesvirus microRNAs in viral infection and replication remains unclear. A viral cluster containing 14 microRNAs is shown to negatively regulate viral replication by targeting the the NF-κB inhibitor IκBα and thereby decreasing NF-κB signalling.