Biology subjects

Shen, J. M.

Publications and source records attributed to Shen, J. M..

2 recordsLinked to original sources

bioRxiv2026

Atypical PI3Ks coordinate chemotaxis, signaling dynamics, and multicellular development in Dictyostelium

Phosphoinositide 3-kinase (PI3K) signaling regulates protrusion, polarity, membrane uptake, and multicellular development in Dictyostelium discoideum, but these functions have been interpreted largely through canonical Class I PI3Ks and PI(3,4,5)P production. This framework does not fully explain how PI3K-dependent pathways attenuate Ras activity, organize PI(3,4)P2-associated polarity states, support cAMP relay, or coordinate development. Here, we identify three atypical PI3K-family enzymes--PikF, PikG, and PikH--as functionally distinct regulators of these processes. PikF constrains Ras-phosphoinositide-actin signaling; pikF- cells show prolonged cAMP-stimulated Ras activation, extended PIP recruitment, delayed PI(3,4)P2 biosensor recovery, elevated peripheral actin activity, impaired chemotactic precision, and delayed abnormal development. PikG acts through a distinct relay-associated pathway: pikG- cells fail to generate endogenous cAMP oscillations, display disrupted ACA polarity, deposit spatially disorganized ACA-positive vesicle trails, and fail to aggregate. PikH, in contrast, supports efficient phagocytic uptake with little effect on acute chemotactic signaling. Kinase-dead rescue experiments show that conserved catalytic lysines are required for PikF- and PikG-dependent development and PikH-dependent uptake. Together, our results reveal that atypical PI3Ks diversify the Dictyostelium PI3K signaling toolkit, separating protrusive signal attenuation, cAMP relay organization, membrane uptake, and multicellular development into distinct kinase-dependent modules.

cell biology↗

bioRxiv2025

Antibody feedback establishes an affinity brake in the germinal center

Recent advances in mRNA vaccine technology have opened the door to novel types of antigen display, but little is yet known as to how B cells recognize and respond to these formats. By delivering an mRNA-LNP encoded membrane-bound immunogen displaying three conserved HIV-1 Envelope (Env) epitopes to knock-in mouse models with B cell receptors (BCRs) of defined affinities, we investigated how epitope-specific competition shapes germinal center (GC) responses. Co-activation of B cells targeting different epitopes did not alter GC kinetics observed in individual activations, but a striking inverse correlation was observed between BCR affinity and GC residence time in either scenario: high-affinity B cells exhibited shorter persistence in GCs, while those with lower affinity to the antigen were maintained. Furthermore, B cells were able to engage in GC reactions at equivalent rates in the presence or absence of clonal lineages binding the same epitope with similar affinities, while higher-affinity clones suppressed lower-affinity counterparts targeting the same epitope. Spatial transcriptomics revealed plasma-like cells within and adjacent to the GC which, together with the detection of early IgG in draining lymph nodes, suggests that local antibody production from these cells may contribute to feedback-driven kinetics. These findings indicate that a self-modulated local antibody feedback loop may act as a "brake" on epitope-specific recognition--dampening further affinity enhancement for high-affinity B cells and facilitating epitope spreading by redirecting the response toward alternative epitopes.

immunology↗