Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015;6(2):89-99.
doi: 10.4161/21541248.2014.989785. Epub 2015 May 5.

Regulation of phagocytosis by Rho GTPases

Yingyu Mao  1 , Silvia C Finnemann
Affiliations
Review

Regulation of phagocytosis by Rho GTPases

Yingyu Mao et al. Small GTPases. 2015.

Abstract

Phagocytosis is defined as a cellular uptake pathway for particles of greater than 0.5 μm in diameter. Particle clearance by phagocytosis is of critical importance for tissue health and homeostasis. The ultimate goal of anti-pathogen phagocytosis is to destroy engulfed bacteria or fungi and to stimulate cell-cell signaling that mount an efficient immune defense. In contrast, clearance phagocytosis of apoptotic cells and cell debris is anti-inflammatory. High capacity clearance phagocytosis pathways are available to professional phagocytes of the immune system and the retina. Additionally, a low capacity, so-called bystander phagocytic pathway is available to most other cell types. Different phagocytic pathways are stimulated by particle ligation of distinct surface receptors but all forms of phagocytosis require F-actin recruitment beneath tethered particles and F-actin re-arrangement promoting engulfment, which are controlled by Rho family GTPases. The specificity of Rho GTPase activity during the different forms of phagocytosis by mammalian cells is the subject of this review.

Keywords: clearance; digestion; engulfment; f-actin recruitment; internalization; membrane receptors; phagocytic cup; phagosome.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Distinct roles and recruitment of Rho GTPases to phagocytic particles at different steps during anti-pathogen phagocytosis via Fc receptors or αMβ2 integrin/CR3 and during clearance phagocytosis mediated by αv integrins and TAM receptors. The time course and distribution of Rho GTPases activation during phagocytosis differs depending on phagocyte receptors as illustrated for FcR-dependent phagocytosis (A), αMβ2-mediated phagocytosis (B), and clearance phagocytosis (C). (B) Note phagocytic particle capture in αMβ2-mediated phagocytosis involves F-actin-rich membrane ruffles that require Rap1-talin signaling, which is also responsible for αMβ2 activation. There are no published studies indicating a role for Rho GTPases in this process. (A-C) Rho GTPases that contribute to the different forms of phagocytosis but with yet unknown localization or specific role are also indicated. Note that most cytoplasmic proteins also involved in phagocytic signaling but not directly implicated in RhoGTPase activity have been omitted from this scheme.
Figure 2.
Figure 2.
Summary diagram of Rho GTPases and their upstream regulators and downstream effectors during clearance phagocytosis mediated by αv integrins and TAM receptors, or during anti-pathogen phagocytosis via Fc receptors, dectin-1, or αMβ2 integrin/CR3. Phagocytosis triggered by engagement of different surface receptors uses complex and overlapping cytosolic proteins upstream and downstream of Rho GTPases. For details and references please consult the main text.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Depraetere V. “Eat me” signals of apoptotic bodies. Nat Cell Biol 2000; 2:E104; PMID:10854338 - PubMed
    1. Reddick LE, Alto NM. Bacteria fighting back: how pathogens target and subvert the host innate immune system. Mol Cell 2014; 54:321-8; PMID:24766896; http://dx.doi.org/10.1016/j.molcel.2014.03.010 - DOI - PMC - PubMed
    1. deCathelineau AM,Henson PM. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays Biochem 2003; 39:105-17; PMID:14585077 - PubMed
    1. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 2007; 131:1124-36; PMID:18083102; http://dx.doi.org/10.1016/j.cell.2007.10.034 - DOI - PubMed
    1. Henson PM. Dampening inflammation. Nat Immunol 2005; 6:1179-81; PMID:16369556 - PubMed

Publication types