News & Views in 2005

Polycystin-1 and -2 — two integral membrane proteins that are mutated in polycystic kidney disease — regulate the cell cycle by preventing nuclear localization of the pro-proliferative helix-loop-helix (HLH) protein Id2. This novel mechanism for restraining Id proteins has important implications for our understanding of the nature of polycystic kidney disease and perhaps other proliferative disorders.

In myotonic dystrophy, a group of RNA-binding factors — the Muscleblind-like proteins — are sequestered by transcripts containing expanded trinucleotide repeats; this sequestration disrupts their proposed physiological function as regulators of alternative splicing. Now, exciting data suggest that Muscleblind-like proteins are also involved in the localization of integrin mRNA.

Neurotransmitter receptors must be targeted to the post-synaptic membrane to perform their function in synaptic transmission. Recent findings reveal a surprising role for heterotrimeric G proteins and their activator, Pins (Partner of Inscuteable), in this important protein targeting event.

Phagocytes may engulf both apoptotic and viable cells via calreticulin on the surface of the target cell, through its interaction with the phagocyte receptor, LRP. In reality, however, only apoptotic cells are engulfed, apparently because their surface ligand CD47 is prevented from activating the inhibitory phagocyte receptor SIRPα.

β-arrestin, a protein known to regulate the signalling, trafficking and degradation of mammalian seven-transmembrane-spanning receptors, has now been identified as a regulator of ubiquitination and degradation of the Notch receptor in Drosophila melanogaster.

How do cells achieve specific and efficient control over a wide spectrum of activities in the context of a limited protein repertoire? A possible answer comes from the recent demonstration that utilization of distinct enzymes by the same A-kinase anchoring protein (AKAP) depends on the AKAP-bound substrate, thus vastly increasing the diversity of AKAP-mediated protein regulation.

Guidance molecules ensure that nerve cells grow in the correct direction during brain development. However, very little is known about the signals transmitted by these molecules. It now seems that netrin-1 — the first guidance molecule discovered — achieves this, in part, through activation of PITPα, a protein involved in lipid transfer.

A new paradigm for gene control has emerged — retaining mRNA in the nucleus to prevent its translation until the gene product is urgently needed.

An increase in the size of the amyloid β-peptide (Aβ42 versus Aβ40) may be a key factor in the pathogenesis of Alzheimer's disease. By altering the activities of enzymes involved in the metabolism of cholesterol and sphingomyelin, an increase in the Aβ42:Aβ40 ratio may cause dysfunction and death of neurons.

Receptor-independent G-protein signalling regulates both the orientation and position of the mitotic spindle during asymmetric cell division. Several new studies show that the targeting of G-protein subunits to the membrane requires Ric-8, pointing to possible novel roles for this protein in both receptor-dependent and -independent pathways.

Anaphase onset is triggered when the protease separase cleaves the cohesive bond that holds replicated sister chromatids together until metaphase. In budding yeast, separase then also regulates mitotic exit. New findings suggest that in vertebrates, separase also participates in cell-cycle regulation, albeit in an unexpected manner.

Plant cortical microtubule arrays influence plant morphogenesis, but the nature of microtubule genesis and self-organization has long puzzled cell biologists. In this issue, Murata and coworkers provide some answers by showing that γ-tubulin nucleates new microtubules along the lengths of existing microtubules, resulting in dispersed 'Y'-branched organizational centres.

Extracellular signalling regulates a plethora of multicellular processes. For microbes, maintaining a specific cell–cell signal in an extracellular environment crowded by other species can be extremely challenging. Two recent papers demonstrate how different bacteria have adapted to avoid, or exploit, species cross-signalling.

How proteins exit the Golgi apparatus on their way to the plasma membrane is poorly understood. Protein kinase D (PKD) is known to regulate this process, but its downstream targets have remained elusive. New work now identifies a previously known player in Golgi dynamics — phosphatidylinositol 4-kinase IIIβ — as a physiological PKD substrate.

Myosin-V transports intracellular cargo along an actin filament, using a 'hand-over-hand' mechanism that moves it forward in 36-nm steps before dissociating. To achieve long run lengths, the stepping of the two myosin heads must be coordinated. Recent evidence favours the idea that this coordination is achieved by intramolecular strain between the heads, so that myosin prefers to pick up its trailing head first to search for a new actin-binding site, and move cargo forward on the actin.