WASH protein drives lysosome–phagosome fusion in neutrophils via syntaxin 19, Scripps Research cell study

Researchers at the Scripps Research Institute (La Jolla, USA) led by Sergio D. Catz, with colleagues from the University of Toronto at Scarborough, the La Jolla Institute for Immunology and other US centers, described in Nature Communications how the actin regulator WASH controls late phagosomal maturation in neutrophils. The paper was published on 7 November 2026. nature.comNature Communicationsnature.comOpen source ↗ It links actin remodeling, lysosomal fusion and bacterial killing.

Neutrophil phagocytosis is crucial for combating infections, but how actin regulates vesicular trafficking during late phagosomal maturation remained obscure, according to the authors. To address this, they used neutrophils lacking WASH (Wiskott-Aldrich Syndrome Protein and Scar Homolog), a regulator of actin nucleation. The approach combined WASH-deficient cells, mass spectrometry of phagolysosomes and a TR-FRET binding assay.

Lysosome fusion and bacterial killing

WASH proved dispensable for particle internalization. Its deficiency, however, impaired lysosome–phagosome fusion and intracellular bacterial killing. In other words, the cells took up particles, but the later steps of processing them were disrupted.

Lysosomes from WASH-deficient neutrophils showed decreased association with actin comets and impaired dynamics. nature.comNature Communicationsnature.comOpen source ↗ Activation of Rac1 rescued lysosomal trafficking but not phagosomal maturation.

Syntaxin 19 as a WASH partner

Mass spectrometry of phagolysosomes and TR-FRET identified atypical syntaxin 19 (STX19) as a WASH binding partner, and WASH recruits STX19 to phagosomes.

Reconstituting WASH in primary neutrophils rescued phagocytosis. Interference with STX19 impaired phagosomal maturation, while STX19 overexpression enhanced it.

The authors conclude that WASH is a central mediator of phagosomal maturation through STX19-mediated membrane fusion and actin-driven lysosomal dynamics. They say this reveals how dysregulated trafficking contributes to immunodeficiency. nature.comNature Communicationsnature.comOpen source ↗ The material describes cell experiments only and gives no clinical data.