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Cellular membranes in eukaryotes are dynamic structures; this is a key property for their roles in numerous cellular processes. In this issue, we present a series of review articles that highlight recent developments in membrane trafficking, and provide an overview of the importance of trafficking events in development and disease.
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.
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.
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.
Wnt signalling regulates development and differentiation through both canonical and non-canonical pathways. Rudnicki and colleagues find that Wnt7a–Fzd7 activates Gαs to promote Akt/mTOR pathway activation, and show that this non-canonical Wnt signalling pathway elicits myofibre hypertrophy in vivo.
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.
Bastiaens and colleagues find that PDEδ can solubilize Ras family small GTPases, resulting in their release from cellular membranes. This concentrates Ras proteins at specific subcellular locations, which promotes their eventual association with the plasma membrane and potentiates Ras-mediated signal transduction.
Ostrowski and colleagues identify a tumour-suppressive pathway in the tumour stroma. They show that PTEN loss in stromal fibroblasts downregulates miR-320, leading to the upregulation of the ETS2 transcription factor and the induction of a secretome that promotes tumour growth, invasion and angiogenesis.
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.
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.