Active nuclear positioning and actomyosin contractility maintain leader cell integrity during gonadogenesis.

Proper distribution of organelles can play an important role in a moving cell's performance. During C. elegans gonad morphogenesis, the nucleus of the leading distal tip cell (DTC) is always found at the front, yet the significance of this localization is unknown.

Chloride intracellular channel (CLIC) proteins function as fusogens.

Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs' function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen.

Therapeutic gene silencing of leads to lethality in genetically unstable cancer cells.

The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with -targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines demonstrated selective vulnerability of genetically unstable cancer cell lines in response to silencing.

Actin-capping protein regulates actomyosin contractility to maintain germline architecture in C. elegans.

Actin dynamics play an important role in tissue morphogenesis, yet the control of actin filament growth takes place at the molecular level. A challenge in the field is to link the molecular function of actin regulators with their physiological function. Here, we report an in vivo role of the actin-capping protein CAP-1 in the Caenorhabditis elegans germline.

Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction.

Contractile epithelial tubes are found in various organs, such as lung airways and blood capillaries. Their ability to sense luminal pressure and respond with adequate contractility is essential for their physiology, and its mis-regulation results in diseases such as asthma and hypertension. Here, we describe a mechanoresponsive regulatory pathway downstream of tissue stretching that controls contraction of the C.

Directed cell invasion and asymmetric adhesion drive tissue elongation and turning in C. elegans gonad morphogenesis.

Development of the C. elegans gonad has long been studied as a model of organogenesis driven by collective cell migration. A somatic cell named the distal tip cell (DTC) is thought to serve as the leader of following germ cells; yet, the mechanism for DTC propulsion and maneuvering remains elusive.

Visualizing and quantifying molecular and cellular processes in Caenorhabditis elegans using light microscopy.

Light microscopes are the cell and developmental biologists' "best friend," providing a means to see structures and follow dynamics from the protein to the organism level. A huge advantage of Caenorhabditis elegans as a model organism is its transparency, which coupled with its small size means that nearly every biological process can be observed and measured with the appropriate probe and light microscope. Continuous improvement in microscope technologies along with novel genome editing techniques to create transgenic probes have facilitated the development and implementation of a dizzying array of methods for imaging worm embryos, larvae, and adults.

Levodopa-responsive dystonia caused by biallelic exon inversion invisible to exome sequencing.

Biallelic pathogenic variants in (), encoding the E3 ubiquitin ligase parkin, lead to early-onset Parkinson's disease. Structural variants, including duplications or deletions, are common in due to their location within the fragile site FRA6E. These variants are readily detectable by copy number variation analysis.

Pyk2 regulates cell-edge protrusion dynamics by interacting with Crk.

Focal adhesion kinase (FAK) is well established as a regulator of cell migration, but whether and how the closely related proline-rich tyrosine kinase 2 (Pyk2) regulates fibroblast motility is still under debate. Using mouse embryonic fibroblasts (MEFs) from Pyk2 mice, we show here, for the first time, that lack of Pyk2 significantly impairs both random and directed fibroblast motility. Pyk2 MEFs show reduced cell-edge protrusion dynamics, which is dependent on both the kinase and protein-protein binding activities of Pyk2.

Probing the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility.

Clustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly 1 µm, and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions.

Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity.

Planar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects.

Mechanosensing in embryogenesis.

Mechanical forces generated by living cells at the molecular level propagate to the cellular and organismal level and have profound consequences for embryogenesis. A direct result of force application is movement, as occurs in chromosome separation, cell migration, or tissue folding. A less direct, but equally important effect of force, is the activation of mechanosensitive signaling, which allows cells to probe their mechanical surrounding and communicate with each other over short and long distances.

Diverse roles of non-muscle myosin II contractility in 3D cell migration.

All is flux, nothing stays still. Heraclitus of Ephesus' characterization of the universe holds true for cells within animals and for proteins within cells. In this review, we examine the dynamics of actin and non-muscle myosin II within cells, and how their dynamics power the movement of cells within tissues.

Germ Granules Govern Small RNA Inheritance.

In C. elegans nematodes, components of liquid-like germ granules were shown to be required for transgenerational small RNA inheritance. Surprisingly, we show here that mutants with defective germ granules can nevertheless inherit potent small RNA-based silencing responses, but some of the mutants lose this ability after many generations of homozygosity.

Reciprocal regulation of actomyosin organization and contractility in nonmuscle cells by tropomyosins and alpha-actinins.

Contractile arrays of actin and myosin II filaments drive many essential processes in nonmuscle cells, including migration and adhesion. Sequential organization of actin and myosin along one dimension is followed by expansion into a two-dimensional network of parallel actomyosin fibers, in which myosin filaments are aligned to form stacks. The process of stack formation has been studied in detail.

biofilms program innate immunity for persistence in .

The adaptive in vivo mechanisms underlying the switch in lifestyles from the infectious form to a dormant form remain unknown. We employed as a heterologous host to understand the temporal dynamics of pathogenesis and to identify its lifestyle form in vivo. We discovered that exists as sessile aggregates, or in vivo biofilms, in the persistently infected gut.

From cell shape to cell fate via the cytoskeleton - Insights from the epidermis.

Animal cells exhibit a wide range of shapes that reflect their diverse functions. Cell shape is determined by a balance between internal and external forces and therefore involves the cytoskeleton and its associated adhesion structures. Cell shape dynamics during development and homeostasis are tightly regulated and closely coordinated with cell fate determination.

The RhoGAP SPV-1 regulates calcium signaling to control the contractility of the Caenorhabditis elegans spermatheca during embryo transits.

Contractility of the nonmuscle and smooth muscle cells that comprise biological tubing is regulated by the Rho-ROCK (Rho-associated protein kinase) and calcium signaling pathways. Although many molecular details about these signaling pathways are known, less is known about how they are coordinated spatiotemporally in biological tubes. The spermatheca of the Caenorhabditis elegans reproductive system enables study of the signaling pathways regulating actomyosin contractility in live adult animals.

Syncytial germline architecture is actively maintained by contraction of an internal actomyosin corset.

Syncytial architecture is an evolutionarily-conserved feature of the germline of many species and plays a crucial role in their fertility. However, the mechanism supporting syncytial organization is largely unknown. Here, we identify a corset-like actomyosin structure within the syncytial germline of Caenorhabditis elegans, surrounding the common rachis.

Principles of Actomyosin Regulation In Vivo.

The actomyosin cytoskeleton is responsible for most force-driven processes in cells and tissues. How it assembles into the necessary structures at the right time and place is an important question. Here, we focus on molecular mechanisms of actomyosin regulation recently elucidated in animal models, and highlight several common principles that emerge.

Cell cycle pacemaker keeps adhesion in step with division.

Adherent cells round up before division but it is unclear how detachment is regulated by the cell cycle. In this issue, Jones et al. (2018.

The myosin light-chain kinase MLCK-1 relocalizes during Caenorhabditis elegans ovulation to promote actomyosin bundle assembly and drive contraction.

We identify the Caenorhabditis elegans myosin light-chain kinase, MLCK-1, required for contraction of spermathecae. During contraction, MLCK-1 moves from the apical cell boundaries to the basal actomyosin bundles, where it stabilizes myosin downstream of calcium signaling. MLCK and ROCK act in distinct subsets of cells to coordinate the timing of contraction.

Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility.

Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled.