FLN-1/filamin is required to anchor the actomyosin cytoskeleton and for global organization of sub-cellular organelles in a contractile tissue.

Actomyosin networks are organized in space, direction, size, and connectivity to produce coordinated contractions across cells. We use the C. elegans spermatheca, a tube composed of contractile myoepithelial cells, to study how actomyosin structures are organized. FLN-1/filamin is required for the formation and stabilization of a regular array of parallel, contractile, actomyosin fibers in this tissue. Loss of fln-1 results in the detachment of actin fibers from the basal surface, which then accumulate along the cell junctions and are stabilized by spectrin. In addition, actin and myosin are captured at the nucleus by the linker of nucleoskeleton and cytoskeleton complex (LINC) complex, where they form large foci. Nuclear positioning and morphology, distribution of the endoplasmic reticulum and the mitochondrial network are also disrupted. These results demonstrate that filamin is required to prevent large actin bundle formation and detachment, to prevent excess nuclear localization of actin and myosin, and to ensure correct positioning of organelles.

Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis.

Individually, dysfunction of both the endoplasmic reticulum (ER) and mitochondria has been linked to aging, but how communication between these organelles might be targeted to promote longevity is unclear. Here, we provide evidence that, in Caenorhabditis elegans, inhibition of the conserved unfolded protein response (UPRER) mediator, activating transcription factor (atf)-6, increases lifespan by modulating calcium homeostasis and signaling to mitochondria. Atf-6 loss confers longevity via downregulation of the ER calcium buffer, calreticulin. ER calcium release via the inositol triphosphate receptor (IP3R/itr-1) is required for longevity, while IP3R/itr-1 gain of function is sufficient to extend lifespan. Highlighting coordination between organelles, the mitochondrial calcium import channel mcu-1 is also required for atf-6 longevity. IP3R inhibition leads to impaired mitochondrial bioenergetics and hyperfusion, which is sufficient to suppress long life in atf-6 mutants. This study reveals the importance of organellar calcium handling as a critical output for the UPRER in determining the quality of aging.

Redox signaling modulates Rho activity and tissue contractility in the Caenorhabditis elegans spermatheca.

Actomyosin-based contractility in smooth muscle and nonmuscle cells is regulated by signaling through the small GTPase Rho and by calcium-activated pathways. We use the myoepithelial cells of the Caenorhabditis elegans spermatheca to study the mechanisms of coordinated myosin activation in vivo. Here, we show that redox signaling modulates RHO-1/Rho activity in this contractile tissue. Exogenously added as well as endogenously generated hydrogen peroxide decreases spermathecal contractility by inhibition of RHO-1, which depends on a conserved cysteine in its nucleotide binding site (C20). Further, we identify an endogenous gradient of H2O2 across the spermathecal tissue, which depends on the activity of cytosolic superoxide dismutase, SOD-1. Collectively, we show that SOD-1-mediated H2O2 production regulates the redox environment and fine tunes Rho activity across the spermatheca through oxidation of RHO-1 C20.

Regulation of Actin Dynamics in the C. elegans Somatic Gonad.

The reproductive system of the hermaphroditic nematode C. elegans consists of a series of contractile cell types-including the gonadal sheath cells, the spermathecal cells and the spermatheca⁻uterine valve-that contract in a coordinated manner to regulate oocyte entry and exit of the fertilized embryo into the uterus. Contraction is driven by acto-myosin contraction and relies on the development and maintenance of specialized acto-myosin networks in each cell type. Study of this system has revealed insights into the regulation of acto-myosin network assembly and contractility in vivo.

Stem Cells: Muscle Cells Enwrap Escaped Germline Stem Cells in C. elegans.

Interactions between the distal tip cell and germline stem cells maintain a proliferative pool of mitotic cells in the Caenorhabditis elegans gonad. A new study shows that escaped germline stem cells induce nearby muscle cells to reach out and wrap around them, forming an ectopic niche similar to the native gonadal germ cell niche.

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.