Biology subjects

Orth, K.

Publications and source records attributed to Orth, K..

3 recordsLinked to original sources

bioRxiv2018

Cancer cell exosomes can initiate malignant cell transformation

Cancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations mediated by intracellular and extracellular cues. We observe that exosomes isolated from pancreatic cancer cells, but not normal pancreatic cells, can initiate the first step of malignant cell transformation. Injection of exosome-initiated transformed cells into mice results in aggressive tumor growth. Using proteomic profiling and DNA sequencing of exosome-treated and transformed cells, we show that cancer cell exosomes act as a classic initiator by causing random genetic changes in recipient cells. Our studies provide new insight into a function of cancer cell exosomes and how they might specifically contribute to orchestrated local cell transformation.\n\nOne Sentence SummaryExosomes function as an initiator of tumor formation.

cancer biology↗

bioRxiv2018

Regulation of the Unfolded Protein Response by BiP AMPylation protects photoreceptors from light-dependent degeneration

In response to environmental, developmental, and pathological stressors, cells engage homeostatic pathways to maintain their function. Among these pathways, the Unfolded Protein Response protects cells from the accumulation of misfolded proteins in the ER. Depending on ER stress levels, the ER-resident Fic protein catalyzes AMPylation or de-AMPylation of BiP, the major ER chaperone and regulator of the Unfolded Protein Response. This work elucidates the importance of the reversible AMPylation of BiP in maintaining the Drosophila visual system in response to stress. After 72 hours of constant light, photoreceptors of fic-null and AMPylation-resistant BiPT366A mutants, but not wild-type flies, display loss of synaptic function, disintegration of rhabdomeres, and excessive activation of ER stress reporters. Strikingly, this phenotype is reversible: photoreceptors regain their structure and function within 72 hours once returned to a standard light:dark cycle. These findings show that Fic-mediated AMPylation of BiP is required for neurons to adapt to transient stress demands.

cell biology↗

bioRxiv2017

T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus

The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH) oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS) production using the Type III Secretion System 2 (T3SS2) effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergo ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production. This is the first example of how a T3SS2 effector contributes to the intracellular survival of V. parahaemolyticus to support the establishment of a protective intracellular replicative niche.

microbiology↗