HtrA1 is upregulated during RANKL-induced osteoclastogenesis,and negatively regulates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK and p38 phosphorylation

Bone remodeling is regulated by secreted factors in the bone microenvironment. However, data regarding osteoclast-derived factors that influence osteoblast differentiation are lacking. Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation. Exogenous addition of recombinant HtrA1 attenuates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK1/2 and p38 phosphorylation in pre-osteoblasts. Our studies imply a unique mode of crosstalk in which HtrA1 is produced by both osteoclasts and osteoblasts and negatively regulates osteoblast differentiation, suggesting that HtrA1 may mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes.     

Stimulated single‐cell force spectroscopy to quantify cell adhesion receptor crosstalk

To control their attachment to substrates and other cells, cells regulate their adhesion receptors. One regulatory process is receptor crosstalk, where the binding of one type of cell adhesion molecule influences the activity of another type. To identify such crosstalk and gain insight into their mechanisms, we developed the stimulated single‐cell force spectroscopy assay. In this assay, the influence of a cells adhesion to one substrate on the strength of its adhesion to a second substrate is examined. The assay quantifies the adhesion of the cell and the contributions of specific adhesion receptors. This allows mechanisms by which the adhesion is regulated to be determined. Using the assay we identified crosstalk between collagen‐binding integrin α₁β₁ and fibronectin‐binding integrin α₅β₁ in HeLa cells. This crosstalk was unidirectional, from integrin α₁β₁ to integrin α₅β₁, and functioned by regulating the endocytosis of integrin α₅β₁. The single‐cell assay should be expandable for the screening and quantification of crosstalk between various cell adhesion molecules and other cell surface receptors.     

Staining of extracellular polymeric substances and cells in bioaggregates

Multiple fluorochrome experiments with as many fluorochromes as possible are desired for exploring the detailed structure of bioaggregates. Spectral peak interference and other practical limitations, however, restrict the maximum number of stains used simultaneously to three. This current study proposes a sixfold labelled scheme to stain the total cells, dead cells, proteins, lipids, and α- and β-polysaccharides in bioaggregates. Two aerobic granule systems, the phenol-fed and the acetate-fed granules, were utilized as the testing samples for demonstrating the use of the proposed scheme.     

The role of protein kinases in the regulation of plant growth and development

We review the role of protein kinases in plant hormone-mediatedsignalling, nutrient signalling and cell cycle control and in the crosstalkbetween these different contributors to plant growth regulation. The areas ofhormone-mediated signalling covered include ABA-mediated responses to osmoticstress, wounding and pathogen attack, as well as ethylene and cytokininsignalling pathways. These areas involve members of several major protein kinasefamilies, including the SNFl-related protein kinase-2 (SnRK2) subfamily, thecalcium-dependent protein kinase (CDPK) family, the mitogen activated protein(MAP) kinase family, the glycogen synthase kinase (GSK)- 3/shaggy family and thereceptor-like protein kinase (RPK) family. In the section on nutrient signallingwe review the role of SnRK1 protein kinases in the global regulation of carbonmetabolism, including aspects of sugar sensing and assimilate partitioning, andwhat is known about nitrogen and sulphur nutrient signalling. In the cell cyclesection, we summarise progress in the elucidation of cell cycle control systemsin plants and discuss the interaction between cell cycle control anddevelopment. We expand further on the hypothesis of crosstalk between differentsignalling pathways in a separate section in which we discuss evidence forinteraction between plant growth regulators and the cell cycle, betweendifferent nutrient signalling pathways, between nutrient and cell cyclesignalling and between nutrient and ABA signalling.     

Autophagy regulates apoptosis by targeting NOXA for degradation

Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation. Inhibiting autophagy increases NOXA protein levels by extending the protein half-life. NOXA accumulation effectively suppresses tumor cell growth by inducing apoptosis, which is further enhanced when p53 is present. Mechanistically, NOXA is hijacked by p62 as autophagic cargo, and its three lysine residues at the C-terminus are necessary for NOXA degradation in lysosomes. Taken together, our study demonstrates that NOXA serves as a bridge in the crosstalk between autophagy and apoptosis and implies that autophagy inhibitors could be an effective therapy for cancer, especially wild-type p53-containing cancer.     

αvβ5/β6 integrin suppression leads to a stimulation of α2β1 dependent cell migration resistant to PI3K/Akt inhibition

Crosstalk between integrins is involved in the regulation of various cell functions including cell migration. Here we identify the interplay between the integrins αvβ5/β6 and α2β1 during cell migration toward type I collagen. Human colon cancer cell lines HT29-D4 and SW480 were used as cell models. To improve our understanding of the consequences of αvβ5/β6 function on α2β1, we decreased the expression of αv integrins by either siRNA or lysosomal targeting strategies or inhibited their function using, as antagonists, blocking antibodies or disintegrins. In all cases, we observed a greatly enhanced α2β1 integrin-dependent cell migration associated with focal adhesion rearrangements and increased outside-in signaling as demonstrated by elevated phosphorylation of focal adhesion kinase and MAPKinase (ERK1 and ERK2). The αvβ5/β6-dependent limitation of α2β1 function could be overridden by TS2/16, an activating anti-β1 antibody. Interestingly, compared to control cells, the pharmacological inhibition of PI3Kinase or the siRNA-mediated knockdown of AKT had little effect on the high α2β1-mediated cell migration observed in the absence of αv integrins or following activation of α2β1 integrins by the TS2/16. These results suggest that integrins αvβ5/β6 repress α2β1 possibly by interfering with their activation process and thereby modify the cell signaling regulation of α2β1-mediated migration.     

Regulation and integration of plant jasmonate signaling: a comparative view of monocot and dicot

The phytohormone jasmonate plays a pivotal role in various aspects of plant life, including developmental programs and defense against pests and pathogens. A large body of knowledge on jasmonate biosynthesis, signal transduction as well as its functions in diverse plant processes has been gained in the past two decades. In addition, there exists extensive crosstalk between jasmonate pathway and other phytohormone pathways, such as salicylic acid(SA) and gibberellin(GA), in co-regulation of plant...     

Mechanisms of talin-dependent integrin signaling and crosstalk

Cells undergo dynamic remodeling of the cytoskeleton during adhesion and migration on various extracellular matrix (ECM) substrates in response to physiological and pathological cues. The major mediators of such cellular responses are the heterodimeric adhesion receptors, the integrins. Extracellular or intracellular signals emanating from different signaling cascades cause inside-out signaling of integrins via talin, a cystokeletal protein that links integrins to the actin cytoskeleton. Various integrin subfamilies communicate with each other and growth factor receptors under diverse cellular contexts to facilitate or inhibit various integrin-mediated functions. Since talin is an essential mediator of integrin activation, much of the integrin crosstalk would therefore be influenced by talin. However, despite the existence of an extensive body of knowledge on the role of talin in integrin activation and as a stabilizer of ECM-actin linkage, information on its role in regulating inter-integrin communication is limited. This review will focus on the structure of talin, its regulation of integrin activation and discuss its potential role in integrin crosstalk. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.