PMID- 22194606
OWN - NLM
STAT- MEDLINE
DCOM- 20120416
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 7
DP  - 2012 Feb 10
TI  - Ras-related GTPases Rap1 and RhoA collectively induce the phagocytosis of 
      serum-opsonized zymosan particles in macrophages.
PG  - 5145-55
LID - 10.1074/jbc.M111.257634 [doi]
AB  - Phagocytosis occurs primarily through two main processes in macrophages: the Fcgamma 
      receptor- and the integrin alphaMbeta2-mediated processes. Complement C3bi-opsonized 
      particles are known to be engulfed through integrin alphaMbeta2-mediated process, which 
      is regulated by RhoA GTPase. C3 toxin fused with Tat-peptide (Tat-C3 toxin), an 
      inhibitor of the Rho GTPases, was shown to markedly inhibit the phagocytosis of 
      serum (C3bi)-opsonized zymosans (SOZs). However, 8CPT-2Me-cAMP, an activator of 
      exchange protein directly activated by cAMP (Epac, Rap1 guanine nucleotide 
      exchange factor), restored the phagocytosis of the SOZs that was previously 
      inhibited by the Tat-C3 toxin. In addition, a constitutively active form of Rap1 
      GTPase (CA-Rap1) also restored the phagocytosis that was previously reduced by a 
      dominant negative form of RhoA GTPase (DN-RhoA). This suggests that Rap1 can 
      replace the function of RhoA in the phagocytosis. Inversely, CA-RhoA rescued the 
      phagocytosis that was suppressed by DN-Rap1. These findings suggest that both 
      RhoA and Rap1 GTPases collectively regulate the phagocytosis of SOZs. In 
      addition, filamentous actin was reduced by the Tat-C3 toxin, which was again 
      restored by 8CPT-2Me-cAMP. Small interfering profilin suppressed the 
      phagocytosis, suggesting that profilin is essential for the phagocytosis of SOZs. 
      Furthermore, 8CPT-2Me-cAMP increased the co-immunoprecipitation of profilin with 
      Rap1, whereas Tat-C3 toxin decreased that of profilin with RhoA. 
      Co-immunoprecipitations of profilin with actin, Rap1, and RhoA GTPases were 
      augmented in the presence of GTPgammaS rather than GDP. Therefore, we propose that 
      both Rap1 and RhoA GTPases regulate the formation of filamentous actin through 
      the interaction between actin and profilin, thereby collectively inducing the 
      phagocytosis of SOZs in macrophages.
FAU - Kim, Jae-Gyu
AU  - Kim JG
AD  - Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, 
      Kangwon-Do 200-702, Republic of Korea.
FAU - Moon, Mi-Young
AU  - Moon MY
FAU - Kim, Hee-Jun
AU  - Kim HJ
FAU - Li, Yi
AU  - Li Y
FAU - Song, Dong-Keun
AU  - Song DK
FAU - Kim, Jun-Sub
AU  - Kim JS
FAU - Lee, Jae-Yong
AU  - Lee JY
FAU - Kim, Jaebong
AU  - Kim J
FAU - Kim, Sung-Chan
AU  - Kim SC
FAU - Park, Jae-Bong
AU  - Park JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111222
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Profilins)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 80295-43-8 (Complement C3b)
RN  - 9010-72-4 (Zymosan)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.5.2 (RhoA protein, mouse)
RN  - EC 3.6.5.2 (rap1 GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Actin Cytoskeleton/genetics/metabolism
MH  - Animals
MH  - Cell Line
MH  - Complement C3b/*pharmacology
MH  - Cyclic AMP/analogs & derivatives/pharmacology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
MH  - Guanosine Diphosphate/pharmacology
MH  - Macrophages/cytology/*metabolism
MH  - Mice
MH  - Mutation
MH  - Phagocytosis/drug effects/*physiology
MH  - Profilins/genetics/metabolism
MH  - Zymosan/*pharmacology
MH  - rap1 GTP-Binding Proteins/genetics/*metabolism
MH  - rho GTP-Binding Proteins/genetics/*metabolism
MH  - rhoA GTP-Binding Protein
PMC - PMC3281652
EDAT- 2011/12/24 06:00
MHDA- 2012/04/17 06:00
PMCR- 2013/02/10
CRDT- 2011/12/24 06:00
PHST- 2011/12/24 06:00 [entrez]
PHST- 2011/12/24 06:00 [pubmed]
PHST- 2012/04/17 06:00 [medline]
PHST- 2013/02/10 00:00 [pmc-release]
AID - S0021-9258(20)48165-7 [pii]
AID - M111.257634 [pii]
AID - 10.1074/jbc.M111.257634 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Feb 10;287(7):5145-55. doi: 10.1074/jbc.M111.257634. Epub 2011 
      Dec 22.