Volume 14 Issue 1, January 2012

New immigration proposals restricting the period of stay for highly skilled migrants in the UK could undermine the future of British science.

The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway, which orchestrates the degradation of ER proteins by the proteasome, involves a plethora of proteins with diverse functions. Using a combination of proteomic and genetic approaches, a recent study provides fresh insights into the organization of the mammalian ERAD interaction network and the functions of its components.

Autophagy can promote both cancer cell survival and death, and the mechanisms by which it mediates these disparate processes are under intense investigation. Autophagosomes are now shown to entrap and promote degradation of the active tyrosine kinase Src, enabling tumour cell survival. The E3 ubiquitin ligase c-Cbl acts as an autophagosome cargo receptor for Src.

Unrestrained Src signalling can be toxic for cancer cells. Wilkinson, Frame and colleagues show that active Src is sequestered in autophagosomes in cancer cells. Inhibition of autophagy induces cancer cell death.

Peterson and colleagues find that the B9 complex localizes to the base of the primary cilia, where it functions as a ciliary diffusion barrier. Mutations in some B9 components are linked to human ciliopathies. The authors show that depleting components of the complex impairs primary cilia formation and inhibits the proper localization and function of signalling receptors in the cilia.

p53 activates Puma-dependent apoptosis and p21-mediated cell-cycle arrest in response to DNA damage. Rudolph and colleagues show that stem-cell functionality in telomerase-deficient mice is improved by the deletion of Puma. Unexpectedly, the accumulation of progenitor cells with damaged short-telomere DNA is not seen in telomerase- and Puma-deficient animals, as p21-mediated cell-cycle arrest is activated to limit the expansion of these cells.

Jürgens and colleagues show that the ARF GEFs GNOM and GNL2 have essential roles in polarized cell growth of root hairs and pollen, respectively. Their findings support an important function for endosomal recycling, rather than polarized secretion, in the targeted delivery of proteins necessary for polar tip growth.

The signalling pathway by which ER damage triggers apoptosis remains unclear. Oakes and colleagues identify CT10-regulated kinase (CRK) as a pro-apoptotic protein induced by ER stress. Such stress leads to the accumulation of cleaved CRK fragments at mitochondria, sensitizing them to cytochrome c release in a cell-free system.

Improperly folded proteins are targeted for destruction through the endoplasmic-reticulum-associated degradation pathway (ERAD). Kopito and colleagues present a high-resolution interaction analysis of the ERAD system in combination with functional genomics, and identify new ERAD components.

Three-colour single-molecule fluorescent in situ hybridization is used by van Oudenaarden and colleagues to show overlapping expression of intestinal stem-cell markers during homeostasis, ageing and regeneration. This approach can help identify putative stem cells in tissues and tumours, and can guide functional studies.

Cellular membranes in eukaryotes are dynamic structures. The budding and fusion of vesicles, as well as the proper delivery of their contents, requires coordinated interactions between coat complexes, adaptor proteins, cargo molecules and cellular machinery including the cytoskeleton. The January 2012 issue of Nature Cell Biologypresents a series of review articles by leading scientists on recent developments in membrane dynamics — including endocytosis, and vesicle biogenesis and transport — and the importance of these processes in development and disease.