Interactions between integrin-mediated adhesions and the extracellular matrix (ECM) are important regulators of cell migration and spreading. However, mechanisms by which extracellular ligands regulate cell migration and spreading in response to changes in substratum concentration are not well understood. Semaphorin 3A (Sema3A) has been shown to inhibit cell motility and alter integrin signaling in various cell types. We propose that Sema3A alters focal adhesions to modulate breast carcinoma cell migration and spreading on substrata coated with different concentrations of ECM. We demonstrate that Sema3A inhibits MDA-MB-231 cell migration and spreading on substrata coated with high concentrations of collagen and fibronectin but enhances migration and spreading at lower concentrations of collagen and fibronectin. Sema3A increases focal adhesion kinase phosphorylation at tyrosine 397 (pFAK397) at focal adhesions on all substratum concentrations of collagen and fibronectin but decreased pFAK397 levels on laminin. Rho-associated protein kinase (ROCK) inhibition blocks the Sema3A-mediated effects on cell migration, spreading, and pFAK397 at focal adhesions when cultured on all concentrations of collagen. These results suggest that Sema3A shifts the optimal level of cell-matrix adhesions to a nonoptimal ECM coating concentration, in particular collagen, to yield maximal cell migration and spreading that may be mediated through a ROCK-dependent mechanism.
In animals, early-life starvation can program gene expression changes that result in profound effects on adult phenotypes. For C. elegans nematodes, passage through the stress-resistant dauer diapause stage due to early-life starvation establishes a cellular memory that manifests as increased metabolism and decreased fecundity compared to continuously developed adults. To further investigate the connection between metabolism and reproduction, we supplemented the diet of postdauer adults with different fatty acids and examined their life history traits. Here, we show that dietary oleic acid (OA) supplementation uniquely increases the fecundity of both postdauer and continuously developed adults in a DAF-12 steroid signaling dependent manner, potentially through the increased expression of fat-7 Δ9-desaturase and vit-2 vitellogen genes. In addition, OA may rescue increased ferroptosis in postdauer germ lines and has complex effects on adult lifespan depending on life history. Together, our results suggest a model where OA modifies DAF-12 activity to positively regulate fecundity, metabolism, and lifespan in adults.
Maintenance of germline function under stress conditions is crucial for species survival. The germ line in many species is especially sensitive to elevated temperature. We have investigated the role of the pocket protein LIN-35 in preserving fertility in Caenorhabditis elegans under moderate temperature stress. We show that lin-35 mutants display several temperature sensitive germline defects, and more severe reductions in brood size at elevated temperatures compared to wild type. This loss of fertility under temperature stress is primarily due to loss of zygotic, but not maternal, LIN-35. Additionally, we have found that expression of LIN-35 is necessary in both the germ line and soma for the preserving fertility under moderate temperature stress. Specifically, while LIN-35 function in the germ line is required for maintaining fertility in hermaphrodites, broad somatic expression of LIN-35 is also necessary for oocyte formation and/or function under moderate temperature stress. Together, our data add to the emerging understanding of the critical role that LIN-35 plays in preserving tissues against stress.
Maintenance of germline function under stress conditions is crucial for species survival. The germline across many species is especially sensitive to elevated temperature stress. We have investigated the role that the pocket protein LIN-35 plays in preserving fertility in C. elegans under moderate high temperature stress. Here we show that lin-35 mutants have a number of temperature sensitive germline defects. The decreased brood size seen at elevated temperatures is more severe in lin-35 mutants than wild type. This loss of fertility under temperature stress is primarily due to loss of zygotic but not maternal LIN-35. Additionally, we have found that expression of LIN-35 is necessary in both the germline and soma for the preserving fertility at elevated temperature. Specifically, germline expressed LIN-35 is primarily what is important for maintaining fertility in hermaphrodites, but broad somatic expression of LIN-35 is also necessary for oocyte formation and/or function at elevated temperatures. Additionally, we found that overexpression of LIN-35 in the germline only can stabilize the formation of P granules in primordial germ cells. Our data adds to the emerging critical role that LIN-35 plays in buffering tissues against stress
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