The N-terminus of the effector Tarp engages the host Hippo pathway.

Unlabelled: () is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector ranslocated ctin-ecruiting hosphoprotein (Tarp), important for entry, has a well-characterized C-terminal region which can polymerize and bundle F-actin.

The N-terminus of the effector Tarp engages the host Hippo pathway.

is an obligate, intracellular Gram-negative bacteria and the leading bacterial STI in the United States. 's developmental cycle involves host cell entry, replication within a parasitophorous vacuole called an inclusion, and induction of host cell lysis to release new infectious particles. During development, manipulates the host cell biology using various secreted bacterial effectors.

The Early Effector Tarp Outcompetes Fascin in Forming F-Actin Bundles .

The intracellular pathogen secretes multiple early effectors into the host cell to promote invasion. A key early effector during host cell entry, Tarp (translocated actin-recruiting phosphoprotein) is comprised of multiple protein domains known to have roles in cell signaling, G-actin nucleation and F-actin bundle formation. , the actin bundles generated by Tarp are uncharacteristically flexible, however, , the biological significance of Tarp-mediated actin bundles remains unknown.

The Infectivity Gene Is Important for Multiple Phases of the Borrelia burgdorferi Enzootic Cycle.

Lyme disease is a multistage inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted through the bite of an infected Ixodes scapularis tick. We previously discovered a B. burgdorferi infectivity gene, , that facilitates mammalian infection by promoting spirochete population expansion in the skin inoculation site.

The Chlamydia trachomatis Tarp effector targets the Hippo pathway.

Chlamydia trachomatis injects bacterial effector proteins into human epithelial cells to facilitate the establishment of new infections. The chlamydial type III secreted effector translocated actin recruiting phosphoprotein (Tarp) has been shown to nucleate and bundle actin filaments. It is also believed to initiate new signaling pathways via an N-terminal phosphorylation domain.

The Borrelia burgdorferi infection critical BBK13 protein forms large oligomers in the spirochete membrane.

Borrelia burgdorferi is the causative agent of Lyme disease, the leading tick-borne illness in the United States. However, due to, in part, to the significant number of proteins of unknown function encoded across the complex fragmented genome, the molecular mechanisms of B. burgdorferi infection remain largely undefined.

Protein phosphatase 1 activity controls a balance between collective and single cell modes of migration.

Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration.

Identifying conserved molecular targets required for cell migration of glioblastoma cancer stem cells.

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and is associated with extensive tumor cell infiltration into the adjacent brain parenchyma. However, there are limited targeted therapies that address this disease hallmark. While the invasive capacity of self-renewing cancer stem cells (CSCs) and their non-CSC progeny has been investigated, the mode(s) of migration used by CSCs during invasion is currently unknown.

RIP2 promotes FcγR-mediated reactive oxygen species production.

Receptor-interacting protein 2 (RIP2) is a kinase that mediates signaling downstream of the bacterial peptidoglycan sensors NOD1 and NOD2. Genetic loss or pharmaceutical inhibition of RIP2 has been shown to be beneficial in multiple inflammatory disease models with the effects largely attributed to reducing proinflammatory signaling downstream of peptidoglycan recognition. However, given the widespread expression of this kinase and its reported interactions with numerous other proteins, it is possible that RIP2 may also function in roles outside of peptidoglycan sensing.

Is Critical for Spirochete Population Expansion in the Skin during Early Infection.

Lyme disease is caused by the spirochete and is transmitted via the bite of an infected tick. enters the skin, disseminates via the bloodstream, and infects various distal tissues, leading to inflammatory sequelae, such as Lyme arthritis and Lyme carditis. linear plasmid 36 (lp36) is critical for mammalian infectivity; however, the full complement of genes on lp36 that contribute to this process remains unknown.

Gene bb0318 Is Critical for the Oxidative Stress Response and Infectivity of Borrelia burgdorferi.

A greater understanding of the molecular mechanisms that Borrelia burgdorferi uses to survive during mammalian infection is critical for the development of novel diagnostic and therapeutic tools to improve the clinical management of Lyme disease. By use of an in vivo expression technology (IVET)-based approach to identify B. burgdorferi genes expressed in vivo, we discovered the bb0318 gene, which is thought to encode the ATPase component of a putative riboflavin ABC transport system.

Dynamic myosin activation promotes collective morphology and migration by locally balancing oppositional forces from surrounding tissue.

Migrating cells need to overcome physical constraints from the local microenvironment to navigate their way through tissues. Cells that move collectively have the additional challenge of negotiating complex environments in vivo while maintaining cohesion of the group as a whole. The mechanisms by which collectives maintain a migratory morphology while resisting physical constraints from the surrounding tissue are poorly understood.

On the role of PDZ domain-encoding genes in Drosophila border cell migration.

Cells often move as collective groups during normal embryonic development and wound healing, although the mechanisms governing this type of migration are poorly understood. The Drosophila melanogaster border cells migrate as a cluster during late oogenesis and serve as a powerful in vivo genetic model for collective cell migration. To discover new genes that participate in border cell migration, 64 out of 66 genes that encode PDZ domain-containing proteins were systematically targeted by in vivo RNAi knockdown.

Par-1 controls myosin-II activity through myosin phosphatase to regulate border cell migration.

Background: Localized actomyosin contraction couples with actin polymerization and cell-matrix adhesion to regulate cell protrusions and retract trailing edges of migrating cells. Although many cells migrate in collective groups during tissue morphogenesis, mechanisms that coordinate actomyosin dynamics in collective cell migration are poorly understood. Migration of Drosophila border cells, a genetically tractable model for collective cell migration, requires nonmuscle myosin-II (Myo-II).

PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells.

Background: Many cells that migrate during normal embryonic development or in metastatic cancer first detach from an epithelium. However, this step is often difficult to observe directly in vivo, and the mechanisms controlling the ability of cells to leave the epithelium are poorly understood. In addition, once cells detach, they must assume a migratory phenotype, involving changes in cytoskeletal and signaling dynamics.