Opinion

The uropod, a protrusion at the rear of amoeboid motile cells such as leukocytes, exemplifies the importance of morphology in cell motility. Although the signalling and structural requirements of uropod formation are being characterized, a clear understanding of uropod function is still lacking.

Coat proteins, such as coat protein I (COPI), couple vesicle formation with cargo sorting to ensure the generation of correctly packaged transport vesicles. Emerging evidence suggests that some long-held views on how COPI vesicles are formed need to be revised.

Endosomes have important roles in processes, including cytokinesis, polarization and migration, in which their function might be distinct from those classically associated with endosomes. We speculate that endosomes function as multifunctional platforms on which unique sets of molecular machines are assembled to suit different cellular roles.

Myofibril assembly results in an array of identical sarcomeres in striated muscle. Recent studies have begun to unravel the mechanisms that set sarcomere spacing and the assembly of initial sarcomere arrays, and point to integrin-dependent adhesion as the starting point for myofibrillogenesis.

Maintenance of organ homeostasis and control of appropriate responses to environmental alterations requires the coordination of cellular functions and tissue organization. This coordination could be achieved by proteins that can have distinct but linked functions on both sides of the plasma membrane.

General principles that govern how microRNAs select their targets and determine their mode of action are being challenged by recent findings in plant and animal systems. A common shortcoming of studies to date has been to address these questions under truein vivoconditions.

Mechanical forces that are exerted on surface-adhesion receptors can be channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. How do these forces act at a distance to induce mechanochemical conversion in the nucleus, and what effects can they have on the cell?

Although most eukaryotic proteins are secreted through the conventional endoplasmic reticulum–Golgi secretory pathway, both cytoplasmic and nuclear proteins have been shown to reach the cell surface by non-conventional transport pathways. The mechanisms and molecular components of unconventional protein secretion are beginning to emerge.

Proto-oncogenic pathways, including the insulin-like growth factor-I (IGF-I), Ras and AKT/PKB pathways, have recently been implicated in the ageing process. In simple organisms, proto-oncogene homologues increase DNA damage, whereas in mice they increase cancer incidence. So, can we prevent cancer by chronic downregulation of pro-ageing pathways?

The question of whether cell death can occur by autophagy cannot yet be answered definitively, although the occurrence of cell death with autophagy is common. The term autophagic cell death should therefore be considered a misnomer until this issue has been resolved.

Cell-cycle transitions in higher eukaryotes are regulated by different cyclin-dependent kinases (CDKs) and cyclins. Recent work using gene-targeted mice has led to a revision of this model and revealed overlapping and essential roles of different CDKs and cyclins.

The 'histone code' hypothesis has inspired rapid advances throughout chromatin biology, and has recently been tapped for its relevance to non-histone proteins. What is the evidence that supports the existence of a protein code? And can this code be used to predict downstream events?

MYCis a potent oncogene that functions as a transcription factor. Extensive research has focused on the mechanism of MYC-induced transcription and on the identification of MYC transcriptional target genes. But does MYC also have transcription-independent roles?

Membrane blebs are considered to be a hallmark of apoptosis; however, blebs are also observed in healthy cells during cytokinesis and cell motility. What are the potential mechanisms by which blebbing can be polarized and translated into movement? And what are the advantages of blebbing motility?

Tumour-necrosis factor receptor-1 (TNFR1) and CD95 can transduce pro-apoptotic and anti-apoptotic signals, but what determines the specificity of signalling events? It is possible that the endosomal compartment functions as a signalling organelle that selectively transmits death signals from TNFR1 and CD95.

Although DNA replication is fundamental to the propagation of cellular life, the bacterial replication machinery is distinct from that used by archaea and eukaryotes. What has been the role of lateral gene transfer by extra-chromosomal elements in shaping the replication machinery during evolution?

Sorting nexins are associated with the early endosomal network and have important functions in endocytosis, sorting and signalling. But how do specific sorting nexins regulate tubular-based endosomal sorting and how do other sorting nexins coordinate sorting with endosomal signalling events?

Deadenylases shorten mRNA poly(A) tails and thereby regulate mRNA translation and decay. Recent studies have shown that these factors form different complexes. The recruitment of multifunctional deadenylase complexes to target mRNAs provides a unique node to control mRNA translation and decay.

The structural maintenance of chromosomes (Smc)5/6 complex has a poorly characterized role in DNA repair. Smc5/6 has been implicated specifically in rDNA stability, but the authors propose that the unidirectional replication of rDNA merely accentuates the genome-wide functions of Smc5/6 in repairing DNA replication errors.

How the building blocks of life came together to form the first membranes and cells is perhaps the biggest unresolved question in biology. A major difference in several proposed models is whether the cytoplasm evolved inside or outside of a liposomal vesicle.