The WASp L272P gain-of-function mutation alters dendritic cell coordination of actin dynamics for migration and adhesion

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Mariana M.S. Oliveira¹  Shin-Yu Kung¹  Hélène D. Moreau²  Mathieu Maurin³  Julien Record¹  Doriane Sanséau²  Susanne Nylén¹  Ana-Maria Lennon-Duménil²  Lisa S. Westerberg¹ 

[1] Department of Microbiology Tumor and Cell Biology, Karolinska Institute;INSERM U932, Institute Curie;Institute Curie, PSL Research University

关键词: actin;    dendritic cells;    microchannels;    migration;    WASp;    X-linked neutropenia;   

DOI  :  10.1002/JLB.1AB0821-013RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome protein (WASp) show reduced directed migration and decreased formation of podosome adhesion structures. We examined DCs expressing a gain-of-function mutation in WASp, WASp L272P, identified in X-linked neutropenia patients. Analysis of WASp L272P DCs was compared to WASp-deficient DCs to examine how WASp activity influences DC migratory responses. In confined space, WASp-deficient DCs had increased migration speed whereas WASp L272P DCs had similar average speed but increased speed fluctuations, reduced displacement, and atypical rounded morphology, compared to wild-type (WT) DCs. Using an ear inflammation model and flow cytometry analysis, WT, WASp-deficient, and WASp L272P DCs were found to migrate in comparable numbers to the draining lymph nodes (LNs). However, histology analysis revealed that migratory DCs of WASp deficient and WASp L272P mice were mainly located in the collagenous capsule of the LN whereas WT DCs were located inside the LN. Analysis of ultrastructural features revealed that WASp L272P DCs had reduced cell area but formed larger podosome structures when compared to WT DCs. Together, our data suggest that WASp activity regulates DC migration and that loss-of-function and gain-of-function in WASp activity lead to different and phenotype-specific DC migratory behavior.

【 授权许可】

CC BY