Work

RABEP1 regulates neutrophil migration via endosomal recycling and actin polymerization

Year: 2026

Type: article

Abstract: Neutrophils are the first responders of our innate immune system, crucial for defense against various infections. The intricate regulation of neutrophil migration is essential for neutrophil function. However, a complete mechanistic understanding is missing. We previously performed a miRNA overexpression screen and identified miR-190 as a potent suppressor of neutrophil migration in zebrafish. Through a second round of small-scale screening using neutrophil-specific knockouts of putative miR-190 targets, we identified that rabep1 (encoding Rabaptin, RAB GTPase binding effector protein 1) is essential for neutrophil motility and chemotaxis in zebrafish. Re-expressing full-length Rabaptin, but not its truncation lacking the Rab4/Rab5 binding domain, rescued cell motility in the knockout. Knocking down RABEP1 in differentiated human leukemia (dHL-60) cells consistently reduced cell motility. RABAPTIN-deficient dHL-60 cells are defective with fast recycling, yet maintain a normal Rab5 GTP level. The RABAPTIN-deficient cells displayed reduced PAK phosphorylation and decreased F-actin levels, yet still appropriately polarized upon chemokine stimulation. Overexpression of dominant-negative Rab4 or Rab5 has a similar inhibitory effect on neutrophil migration. Our data suggest that RABAPTIN drives endosomal recycling, Rac activation, and leading-edge actin polymerization, providing significant insights into the role of the endocytic pathway in neutrophil motility.

Source: Journal of Leukocyte Biology

DOI: 10.1093/jleuko/qiaf174