Next Article in Journal
The P2X7 Receptor Stimulates IL-6 Release from Pancreatic Stellate Cells and Tocilizumab Prevents Activation of STAT3 in Pancreatic Cancer Cells
Next Article in Special Issue
Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases
Previous Article in Journal
The Molecular Aspect of Nephrolithiasis Development
Previous Article in Special Issue
Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research
Article

Acute RhoA/Rho Kinase Inhibition Is Sufficient to Restore Phagocytic Capacity to Retinal Pigment Epithelium Lacking the Engulfment Receptor MerTK

Center for Cancer, Genetic Diseases, and Gene Regulation, Department of Biological Sciences, Larkin Hall, Fordham University, 441 East Fordham Road, Bronx, NY 10458, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Igor Weber and Vedrana Filić
Cells 2021, 10(8), 1927; https://doi.org/10.3390/cells10081927
Received: 13 June 2021 / Revised: 26 July 2021 / Accepted: 26 July 2021 / Published: 29 July 2021
(This article belongs to the Special Issue Rho family of GTPases in Model Organisms and Systems)
The diurnal phagocytosis of spent photoreceptor outer segment fragments (POS) by retinal pigment epithelial (RPE) cells is essential for visual function. POS internalization by RPE cells requires the assembly of F-actin phagocytic cups beneath surface-tethered POS and Mer tyrosine kinase (MerTK) signaling. The activation of the Rho family GTPase Rac1 is necessary for phagocytic cup formation, and Rac1 is activated normally in MerTK-deficient RPE. We show here that mutant RPE lacking MerTK and wild-type RPE deprived of MerTK ligand both fail to form phagocytic cups regardless of Rac1 activation. However, in wild-type RPE in vivo, a decrease in RhoA activity coincides with the daily phagocytosis burst, while RhoA activity in MerTK-deficient RPE is constant. Elevating RhoA activity blocks phagocytic cup formation and phagocytosis by wild-type RPE. Conversely, inhibiting RhoA effector Rho kinases (ROCKs) rescues both F-actin assembly and POS internalization of primary RPE if MerTK or its ligand are lacking. Most strikingly, acute ROCK inhibition is sufficient to induce the formation and acidification of endogenous POS phagosomes by MerTK-deficient RPE ex vivo. Altogether, RhoA pathway inactivation is a necessary and sufficient downstream effect of MerTK phagocytic signaling such that the acute manipulation of cytosolic ROCK activity suffices to restore phagocytic capacity to MerTK-deficient RPE. View Full-Text
Keywords: F-actin; MerTK; phagocytosis; TAM receptors; retinal pigment epithelium; RhoA; ROCK F-actin; MerTK; phagocytosis; TAM receptors; retinal pigment epithelium; RhoA; ROCK
Show Figures

Graphical abstract

MDPI and ACS Style

Mao, Y.; Finnemann, S.C. Acute RhoA/Rho Kinase Inhibition Is Sufficient to Restore Phagocytic Capacity to Retinal Pigment Epithelium Lacking the Engulfment Receptor MerTK. Cells 2021, 10, 1927. https://doi.org/10.3390/cells10081927

AMA Style

Mao Y, Finnemann SC. Acute RhoA/Rho Kinase Inhibition Is Sufficient to Restore Phagocytic Capacity to Retinal Pigment Epithelium Lacking the Engulfment Receptor MerTK. Cells. 2021; 10(8):1927. https://doi.org/10.3390/cells10081927

Chicago/Turabian Style

Mao, Yingyu, and Silvia C. Finnemann 2021. "Acute RhoA/Rho Kinase Inhibition Is Sufficient to Restore Phagocytic Capacity to Retinal Pigment Epithelium Lacking the Engulfment Receptor MerTK" Cells 10, no. 8: 1927. https://doi.org/10.3390/cells10081927

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop