Reviews & Analysis

Work in this issue advances our understanding of how the small G protein Cdc42 functions to polarize budding yeast. Remarkably, Cdc42 can polarize in the absence of upstream cues or positive feedback from the cytoskeleton. Polarization requires the scaffold protein Bem1 and cycling of Cdc42 between its GTP- and GDP-bound states.

Apoptosis is a feature of many diseases and is critical for the sculpting and maintenance of tissues. New work demonstrates that calcium released from the endoplasmic reticulum synchronizes the mass exodus of cytochrome c from the mitochondria, a phenomenon that coordinates apoptosis.

Some kinesin motors can move along a microtubule for many hundred steps without dissociating. These motors are dimers, but precisely how the two motor domains are coordinated during stepping is still the subject of debate. A novel experimental approach offers new insights.

Polarized epithelia require selective protein trafficking to establish and preserve distinct apical and basolateral surfaces. Recent work indicates that in polarized cells, the AP-1B clathrin adaptor recognizes certain basolateral targeting signals in an endosomal compartment where it seems to not only capture cargo but also promote recruitment of targeting and fusion machinery, ensuring accurate polarized sorting.

The choice of ubiquitination substrates of Cul1- and Cul2-based E3 ubiquitin protein ligase complexes is dictated by the identity of their substrate-specific adaptors, known as F-box and BC-box proteins, respectively. Recent work suggests that members of the large family of BTB-domain proteins define a new class of substrate-specific adaptors of Cul3-based E3 complexes. This finding places many signalling pathways in which BTB-domain proteins participate under direct control of the ubiquitination pathway.

During organogenesis different cells must recognize and adhere to each other in a complicated orchestration of cell movements that requires intricate regulation of cell adhesions. A Maf transcription factor, Traffic jam, has been found to regulate a panel of cell adhesion molecules, and the interactions between germ cells and somatic cells to shape the mature gonad.

Bone-marrow-derived stem cells have been shown to contribute to Purkinje neurons in the cerebellum of adult humans and mice. A new study identifies cell fusion as the mechanism underlying this phenomenon, and shows that the bone marrow cell portion of the resulting binucleate heterokaryons acquires the morphological and molecular characteristics of Purkinje neurons over time.

The most interesting discoveries are often those that couple distinct fields of science in unexpected ways. The marriage of the nuclear pore complex to the kinetochore and spindle checkpoint regulation is a recent example, raising the question of why such divergent processes as mitosis and nuclear transport use common proteins.

Rab GTPases function at all stages of the endocytic and exocytic pathways. Although it is clear that each Rab is required for specific transport events, the process by which they are recruited to distinct compartments along the membrane trafficking pathway has remained obscure. Recent data suggests that a member of the Yip family is important for the membrane recruitment of endosomal Rabs.

During cell-contact-mediated repulsion, an initially adhesive interaction between a receptor and its ligand ultimately results in a repulsive response that causes the cells to separate. Two studies looking at the case of Eph receptors and ephrins now identify a crucial role for endocytosis in this enigmatic process.

During development, tissue growth is controlled by coordinated cellular growth and apoptosis. A series of recent papers describes a newly identified Drosophila gene, hippo, that restricts excessive growth during development by both limiting cell cycle progression and promoting susceptibility to apoptosis. Therefore, hippo may coordinate the regulation of cell division and cell death.

Mammalian sperm require activation within the female reproductive tract to fertilize eggs, and bicarbonate is essential for this process in vitro. A recent study implicates the cystic fibrosis transmembrane regulator (CFTR) as a possible regulator for bicarbonate release in vivo.

The putative tumour suppressor LKB1/XEEK1 (Xenopus egg and embryo kinase 1) has been implicated in many cellular processes and signalling pathways. Now, XEEK1 is found to exist in a complex with GSK3 (glycogen synthase kinase 3) and protein kinase C ζ (PKCζ), resulting in increased Wnt signal transduction during embryonic development. This discovery positions XEEK1 as a potential intersection point for crosstalk between Wnt and other pathways.