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Arp2/3 Complex Is Required for Macrophage Integrin Functions but Is Dispensable for FcR Phagocytosis and In Vivo Motility.


ABSTRACT: The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2-/-) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2-/- macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and ?M/?2 integrin localization are compromised in Arpc2-/- cells. Using an in vivo system to observe endogenous monocytes migrating toward full-thickness ear wounds we found that Arpc2-/- monocytes maintain cell speeds and directionality similar to control. Our work reveals that the Arp2/3 complex is not a general requirement for phagocytosis or chemotaxis but is a critical driver of integrin-dependent processes. We demonstrate further that cells lacking Arp2/3 complex function in vivo remain capable of executing important physiological responses that require rapid directional motility.

SUBMITTER: Rotty JD 

PROVIDER: S-EPMC5601320 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Arp2/3 Complex Is Required for Macrophage Integrin Functions but Is Dispensable for FcR Phagocytosis and In Vivo Motility.

Rotty Jeremy D JD   Brighton Hailey E HE   Craig Stephanie L SL   Asokan Sreeja B SB   Cheng Ning N   Ting Jenny P JP   Bear James E JE  

Developmental cell 20170831 5


The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2<sup>-/-</sup>) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2<sup>-/-</sup> macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent  ...[more]

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