PMID- 32761234
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20211023
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 15
DP  - 2020 Aug 11
TI  - Neutrophils lacking ERM proteins polarize and crawl directionally but have 
      decreased adhesion strength.
PG  - 3559-3571
LID - 10.1182/bloodadvances.2020002423 [doi]
AB  - Ezrin/radixin/moesin (ERM) proteins are adaptors that link the actin cytoskeleton 
      to the cytoplasmic domains of membrane proteins. Leukocytes express mostly moesin 
      with lower levels of ezrin but no radixin. When leukocytes are activated, ERMs 
      are postulated to redistribute membrane proteins from microvilli into uropods 
      during polarization and to transduce signals that influence adhesion and other 
      responses. However, these functions have not been tested in leukocytes lacking 
      all ERMs. We used knockout (KO) mice with neutrophils lacking ezrin, moesin, or 
      both proteins (double knockout [DKO]) to probe how ERMs modulate cell shape, 
      adhesion, and signaling in vitro and in vivo. Surprisingly, chemokine-stimulated 
      DKO neutrophils still polarized and redistributed ERM-binding proteins such as 
      PSGL-1 and CD44 to the uropods. Selectin binding to PSGL-1 on moesin KO or DKO 
      neutrophils activated kinases that enable integrin-dependent slow rolling but not 
      those that generate neutrophil extracellular traps. Flowing neutrophils of all 
      genotypes rolled normally on selectins and, upon chemokine stimulation, arrested 
      on integrin ligands. However, moesin KO and DKO neutrophils exhibited defective 
      integrin outside-in signaling and reduced adhesion strength. In vivo, DKO 
      neutrophils displayed normal directional crawling toward a chemotactic gradient, 
      but premature detachment markedly reduced migration from venules into inflamed 
      tissues. Our results demonstrate that stimulated neutrophils do not require ERMs 
      to polarize or to move membrane proteins into uropods. They also reveal an 
      unexpected contribution of moesin to integrin outside-in signaling and adhesion 
      strengthening.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Panicker, Sumith R
AU  - Panicker SR
AD  - Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 
      Oklahoma City, OK; and.
FAU - Yago, Tadayuki
AU  - Yago T
AD  - Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 
      Oklahoma City, OK; and.
FAU - Shao, Bojing
AU  - Shao B
AD  - Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 
      Oklahoma City, OK; and.
FAU - McEver, Rodger P
AU  - McEver RP
AD  - Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 
      Oklahoma City, OK; and.
AD  - Department of Biochemistry and Molecular Biology, University of Oklahoma Health 
      Sciences Center, Oklahoma City, OK.
LA  - eng
GR  - P30 GM114731/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (ezrin)
RN  - 144131-77-1 (moesin)
RN  - 144517-21-5 (radixin)
SB  - IM
MH  - Animals
MH  - Cytoskeletal Proteins
MH  - *Membrane Proteins/genetics
MH  - Mice
MH  - Microfilament Proteins
MH  - *Neutrophils
PMC - PMC7422121
COIS- Conflict-of-interest disclosure: R.P.M. is a cofounder of Selexys 
      Pharmaceuticals, now part of Novartis AG, and of Tetherex Pharmaceuticals. The 
      remaining authors declare no competing financial interests.
EDAT- 2020/08/08 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/08/06
CRDT- 2020/08/08 06:00
PHST- 2020/05/22 00:00 [received]
PHST- 2020/06/28 00:00 [accepted]
PHST- 2020/08/08 06:00 [entrez]
PHST- 2020/08/08 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/08/06 00:00 [pmc-release]
AID - S2473-9529(20)31583-4 [pii]
AID - 2020/ADV2020002423 [pii]
AID - 10.1182/bloodadvances.2020002423 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Aug 11;4(15):3559-3571. doi: 10.1182/bloodadvances.2020002423.