Saini V et al. (2011) Int J Pharm "Sufficiency of a single administration of filarial antigens adsorbed on polymeric lamellar substrate particles of poly (L-lactide) for immunization."

Kohli DV, Verma SK, Sahoo MK, Saini V, Murthy PK

[Int J Pharm, 2011]

A majority of antigens require repeated administration to ensure development of adequate humoral and cell mediated immune response. To minimize the number of administrations required, we investigated the utility of biodegradable polymeric lamellar substrate particles of poly (l-lactide) (PLSP) as adjuvant for filarial antigen preparations. PLSP was prepared and characterized and Brugia malayi adult worm extract (BmA) and its SDS-PAGE resolved 54-68 kDa fraction F6 were adsorbed on to PLSP. Swiss mice received a single injection of PLSP-F6, PLSP-BmA, FCA-F6, FCA-BmA and two doses of the plain antigens. Specific IgG, IgG1, IgG2a, IgG2b and IgE levels in serum, IFN-, TNF- and nitric oxide (NO) release from cells of the immunized animals in response to antigen challenge were studied. The average size of PLSP particles was <10 m and its % antigen adsorption efficacy was 60.4, 55.2 and 61.6 for BSA, BmA and F6, respectively. Single injection of PLSP-F6 or PLSP-BmA produced better immune responses compared to one injection of FCA-F6/BmA or two injections of plain F6 or BmA. Moreover, PLSP-F6 produced much better response than PLSP-BmA. These data demonstrate for the first time that PLSP is a superior immunoadjuvant for enhancing the immune response to filarial BmA and F6 molecules and obviates the need for multiple immunization injections.

Pandey A et al. (2017) Cell Adh Migr "The unc-53 gene negatively regulates rac GTPases to inhibit unc-5 activity during Distal tip cell migrations in C. elegans."

Pandey GK, Khurana JP, Yadav V, Pandey A, Sharma A

[Cell Adh Migr, 2017]

The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the two known negative regulators of ced-10/Rac signaling. Our genetic analysis supports the model, where abl-1 negatively regulates unc-53 during DTC migrations and requirement of unc-53 function during both AP and DV DTC migrations could be due to unc-53 mediated regulation of unc-5 activity.

Feng G et al. (2016) EMBO J "Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans."

Ou G, Lin Q, Dong MQ, Feng G, Li WJ, Zhu Z, Chai Y

[EMBO J, 2016]

Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior-posterior body axis via the inhibition of dorsal-ventral (DV) migration. Ectopic DV polarization was also demonstrated in gain-of-function mutant animals for C.elegans RhoG MIG-2. We identified serine 139 of MIG-2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG-2(S139) Live imaging analysis of genome-edited animals indicates that MIG-2(S139) phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild-type cells, while MIG-2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG-mediated polarization. Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility.

Schonegg S et al. (2014) Genesis "Timing and mechanism of the initial cue establishing handed leftright asymmetry in Caenorhabditis elegans embryos."

Hyman AA, Schonegg S, Wood WB

[Genesis, 2014]

By the six-cell stage, embryos of Caenorhabditis elegans are morphologically LR asymmetric with an invariant handedness that persists throughout development. We used intracellular markers to ask whether breaking of LR symmetry could be observed at earlier stages. Observation of two- to three-cell embryos carrying intracellular markers indicated that LR symmetry is broken concomitantly with establishment of DV axis polarity during division of the anterior AB cell. The AB cleavage furrow initiates asymmetrically and always from the left, suggesting LR differences in the AB cell cortex. An invariantly handed cortical rotation observed earlier during first cleavage implies that the one-cell embryo has an intrinsic chirality. We propose that LR differences in the cortex could result from mechanical forces on asymmetric components of a chiral cortical network during the off-axis elongation of the AB-cell spindle prior to AB cleavage.