Neurodegeneration

Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Donaldson, K. M. et al. Proc. Natl Acad. Sci. USA 100, 8892–8897 (2003)

In many neurodegenerative diseases, ubiquitin (Ub)-positive protein aggregates are present in affected neurons. But how these Ub-positive protein aggregates are formed is unclear. Donaldson et al. now show that two Ub-binding proteins, Atx-3 and p62/Sequestosome-1, which form aggregates in affected neurons, require the functional Ub-binding motifs for localization into aggregates. This recruitment, through Ub, could contribute to the pathogenesis of neurodegenerative diseases.

Apoptosis

Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Micheau, O. & Tschopp, J. Cell 114, 181–190 (2003)

Signalling by the TNF-receptor I (TNFR1) can either promote cell survival or cause apoptosis. How the cell decides between the two pathways can now be explained, as TNFR1-induced apoptosis requires the formation of two sequential complexes. First, complex I forms, which comprises TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2, and it signals activation of nuclear factor (NF)-κB. Unless NF-κB activation induces FLIPL — which inhibits the caspase-8 — procaspases-8 and -10 are recruited to form complex II, and this results in apoptosis.

Cell adhesion

Integrin–ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus. Marsden, M. & DeSimone, D. W. Curr. Biol. 13, 1182–1191 (2003)

Convergent extension is a fundamental developmental process that underlies cell and tissue movements in morphogenesis. This paper sheds light on the underlying molecular mechanisms, by showing that fibronectin–integrin interactions are essential for cell intercalation behaviour and axial extension in Xenopus. Integrin modulation of cadherin adhesion influences morphogenetic movements within local areas that are defined by the fibronectin extracellular matrix.

Nuclear transport

RanGTP mediates nuclear pore complex assembly. Walther, T. C. et al. Nature 424, 689–694 (2003)

The multi-talented GTPase Ran has roles in nuclear transport, spindle formation and nuclear-envelope assembly. Walther et al. now uncover details of another of its suspected functions — in nuclear pore complex (NPC) formation. RanGTP production targets a subset of nucleoporins to the chromatin by dissociating them from importin-β, promotes the association between nucleoporin sub-complexes and triggers NPC insertion into membranes.