Issues

Secretory proteins are targeted for secretion by sequences in their mature domains, as well as by N-terminal signal peptides.

Antonina Roll-Mecak studies how tubulin diversity modulates the specificity, complexity, and function of the microtubule network.

Vizcarra and Quinlan discuss new results from the Kovar group describing the mode of nucleation of bacterial WH2 domain actin nucleators.

Sidor and Röper preview a study by Simões et al. that describes the function of myosin II in modulating apical constriction and cell contact loss during neuroblast ingression.

Das and Knust preview work from Perez-Mockus et al. describing how Neuralized controls Crumbs and epithelial cell polarity via distinct Stardust isoforms.

Keeler and Deppmann preview work from Foldi et al. that describes some of the cellular mechanisms governing the induction of survival and death decisions by Drosophila neurotrophic factors.

Molday and Goldberg discuss work by Salinas et al. describing formation of the light-sensing outer segment organelle of photoreceptor cells.

This review by Morimoto and colleagues examines mechanisms by which protein homeostasis (proteostasis) is achieved in multicellular organisms and discusses the implications for health and disease.

During mitosis, cells monitor kinetochore–microtubule attachments as a means of detecting errors. Although end-on attachments have not been observed in Caenorhabditis elegans oocytes, Davis-Roca et al. now report that these cells alter key aspects of anaphase progression in the presence of meiotic defects, revealing a new strategy for error detection during cell division.

Mutations in centrosomal and spindle checkpoint proteins cause microcephaly in mammals. Poulton et al. explore their roles in the Drosophila brain. Although loss of either alone is tolerated, combined loss leads to massive mitotic errors, increased cell death, and dramatic perturbations of brain development.

How the bacterial virulence factors VopL/F from Vibrio catalyze actin nucleation is unclear. Using multicolor TIRF microscopy imaging, Burke et al. find that VopL and VopF stimulate actin assembly via identical pointed-end nucleation mechanisms.

König et al. perform time-resolved electron tomographic reconstructions to decipher the membrane remodeling events in abscission, the final step of cytokinesis, in Caenorhabditis elegans and find that completion of the scission process requires actomyosin-driven membrane remodeling, but not the ESCRT machinery.

During ciliogenesis, the daughter centriole is found next to the mother, but its role in this process is not known. Loukil et al. show that a daughter centriole is necessary for primary cilia formation by promoting Neurl-4–dependent removal of the negative ciliogenesis regulator CP110 from the mother.

Mutations in WDR81, a regulator of the endosomal–lysosomal pathway, are implicated in CAMRQ2 syndrome, which manifests as cerebellar ataxia, mental retardation, and quadrupedal locomotion in patients. In this study, Liu et al. uncover a distinct function of WDR81 in the clearance of ubiquitinated and aggregated proteins by autophagy.

The GTPase atlastin mediates homotypic membrane ER fusion through trans-dimerization between GTPase heads. Winsor et al. use a mutagenesis approach to show that, upon contact between atlastin heads, the proteins concurrently display GTP hydrolysis-catalyzed head-to-head dimerization and a crossover conformational shift, and these changes energize fusion.

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disease caused by mutations in many genes, including those encoding spastin, strumpellin, or REEP1. Allison et al. show that similar lysosomal phenotypes are associated with mutations in different classes of HSP proteins and suggest that defective ER–endosome contacts and endosome tubule fission may be a common cause of axon degeneration in the disease.

Secretory preproteins contain a mature domain fused to a signal peptide that targets the protein to the translocase, which mediates secretion. In this study, the authors show that the mature domains bear independent targeting signals (MTS) that consist of multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that are essential for proper secretion.

Ding et al. characterize the function of the F-actin bundling protein plastin in the Caenorhabditis elegans zygote. They demonstrate that plastin is important for optimal connectivity in the cortical actomyosin network that drives large-scale contractile processes such as polarization and cytokinesis.

Drosophila neural stem cells, or neuroblasts, ingress from the neuroepithelium in an EMT-like process, during which the apical cell domain is lost. Apical constriction of neuroblasts and the serial loss of cell–cell contacts require periodic pulses of actomyosin that cause progressively stronger ratcheted contractions of the neuroblast apical cortex.

The E3 ubiquitin ligase Neuralized is shown to interact with a subset of the Stardust isoforms to regulate the endocytosis of the apical protein Crumbs and thereby promote epithelial remodeling during Drosophila development.

A three-tier mechanism involving distinct neurotrophin family ligand forms, different Toll receptors, and different adaptors regulates both cell survival and death. This rich mechanism confers cell number plasticity and could underlie structural plasticity in the nervous system and structural integrity, homeostasis, and regeneration in wider contexts.

The mechanisms of stem cell niche formation are largely unknown. Lai et al. show that proper formation of the Drosophila melanogaster adult ovarian germline stem cell niche requires a Hedgehog gradient, signaling through a Ci–Traffic Jam–E-cadherin regulatory axis, to direct segregation of intermingled cells by differential cell affinity.

Integrin-mediated cellular functions require integrin activation by the proteins Kindlin-2 and Talin. Wei et al. show that the E3 ligase Smurf1 permits precise modulation of integrin-mediated adhesion by interacting with and promoting Kindlin-2 ubiquitination and degradation.

The development of novel therapies to promote wound healing is hindered by our poor understanding of how different integrins function together in the epidermis. Longmate et al. show that cross-suppression by integrins within the epidermis controls paracrine signals that regulate wound angiogenesis. Integrin α9β1 suppresses the proangiogenic functions of α3β1 during late-stage wound healing, leading to the normalization of blood vessel density in the wound bed.

Visual signal transduction occurs on the surface of membrane discs stacked inside the ciliary outer segment of photoreceptor cells. Salinas et al. show that discs are formed from ciliary ectosomes whose release is blocked by the protein peripherin/RDS. This explains how photoreceptors transform their primary cilia into the light-sensing outer segment organelle.