STIM1 at the plasma membrane: A novel Molecular regulator of B cell migration

Original title: STIM1 at the plasma membrane: A novel Molecular regulator of B cell migration.

Cell migration is a fundamental process required for effective immune responses, relying on both amoeboid movement and chemotaxis.

By LE GOUX, Buscaglia, Mainguy +3Oct 19, 2026

Score████░░░░░░4.5

Caveats

Preprint; not yet peer reviewed.

VerdictWorth a reader's time today.

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Abstract

Cell migration is a fundamental process required for effective immune responses, relying on both amoeboid movement and chemotaxis. Among chemotactic pathways, the CXCL12/CXCR4 axis plays a pivotal role in guiding B cell migration. While essential under physiological conditions, this pathway is frequently dysregulated in pathological contexts such as Chronic Lymphocytic Leukemia (CLL) and Systemic Lupus Erythematosus (SLE), where altered CXCR4 expression enhances B cell retention, survival, and tissue infiltration. Calcium signaling is central to B cell migration, notably through Store-Operated Calcium Entry (SOCE), STIM1 located at the endoplasmic reticulum (ER) membrane and Orai1 calcium channels. Although STIM1 is traditionally studied as an ER protein regulating SOCE, early findings and recent work from our group indicate that STIM1 is also present at the plasma membrane (STIM1PM), where it displays a dual topology and contributes to constitutive calcium entry (CCE). The function of STIM1PM pool in B cell migration remains unknown. Here, we demonstrate that both STIM1ER and Orai1 are required for CXCL12-induced migration of B cells. Importantly, we provide the first evidence that STIM1PM, exhibiting N?terminal and C?terminal orientations, actively regulates B cell migration independently of SOCE. We show that STIM1PM controls CCE and modulates intercellular interactions, thereby influencing chemotactic responses. Targeting STIM1PM domains significantly impairs B cell migration, highlighting its potential as a novel therapeutic target in diseases characterized by aberrant B cell trafficking. Our findings uncover an unanticipated role for STIM1PM and open new perspectives on calcium?dependent and calcium?independent mechanisms of B cell migration.

N. LE GOUX, P. Buscaglia, A. Mainguy, M. Hus, M. Blery, O. Mignen

The editor's rubric

Heuristic review

Leverage3 / 5: A method or resource many groups across the field will adopt within a year.; 24% of this desk’s rubric
Magnitude3 / 5: Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.; 16% of this desk’s rubric
Evidence3 / 5: Solid: multiple benchmarks or cohorts, ablations, fair baselines, released code or data.; 20% of this desk’s rubric
Novelty3 / 5: A genuinely new approach to an open problem.; 20% of this desk’s rubric
Trajectory2 / 5: Some room to improve with obvious engineering.; 10% of this desk’s rubric
Stakes3 / 5: Meaningful benefit to many people within a few years.; 10% of this desk’s rubric

Dimension	Level	Weight	What that level means
Leverage	███░░ 3	24%	A method or resource many groups across the field will adopt within a year.
Magnitude	███░░ 3	16%	Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.
Evidence	███░░ 3	20%	Solid: multiple benchmarks or cohorts, ablations, fair baselines, released code or data.
Novelty	███░░ 3	20%	A genuinely new approach to an open problem.
Trajectory	██░░░ 2	10%	Some room to improve with obvious engineering.
Stakes	███░░ 3	10%	Meaningful benefit to many people within a few years.

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: method (we report); firsts (first); design (phase 3); verification (independent replication); stakes (mortality, major disease, prevention or cure).

How the score was computed

rank-2026-10-18

Score████░░░░░░4.5

Score = 10 × (75% × adjusted merit / 10 + 15% × attention + 10% × freshness)

Desks place stronger verdicts first, then use this score to order work within the same verdict.

Merit: 5.8 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 4.8 / 10; Shrunk toward the desk prior by editor confidence (44%).
Attention: 0%; Citations, upvotes, points, mentions.
Freshness: 88%; Half-life decay since publication.

No attention signals recorded yet.

The record

Reviewed by heuristic-v7 on Oct 20, 2026, 05:48 UTC. Paper type: method.
Categories: cell biology
TOP, No.3 in the Front page edition of October 20, 2026.
LEAD, No.1 in the Biology edition of October 20, 2026.