PMID- 37533258
OWN - NLM
STAT- Publisher
LR  - 20231122
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Linking)
DP  - 2023 Aug 1
TI  - Lipid-driven interleaflet coupling of plasma membrane order regulates FcepsilonRI 
      signaling in mast cells.
LID - S0006-3495(23)00478-2 [pii]
LID - 10.1016/j.bpj.2023.07.027 [doi]
AB  - Interleaflet coupling-the influence of one leaflet on the properties of the 
      opposing leaflet-is a fundamental plasma membrane organizational principle. This 
      coupling is proposed to participate in maintaining steady-state biophysical 
      properties of the plasma membrane, which in turn regulates some transmembrane 
      signaling processes. A prominent example is antigen (Ag) stimulation of signaling 
      by clustering transmembrane receptors for immunoglobulin E (IgE), FcepsilonRI. This 
      transmembrane signaling depends on the stabilization of ordered regions in the 
      inner leaflet for sorting of intracellular signaling components. The resting 
      inner leaflet has a lipid composition that is generally less ordered than the 
      outer leaflet and that does not spontaneously phase separate in model membranes. 
      We propose that interleaflet coupling can mediate ordering and disordering of the 
      inner leaflet, which is poised in resting cells to reorganize upon stimulation. 
      To test this in live cells, we first established a straightforward approach to 
      evaluate induced changes in membrane order by measuring inner leaflet diffusion 
      of lipid probes by imaging fluorescence correlation spectroscopy, by imaging 
      fluorescence correlation spectroscopy (ImFCS), before and after 
      methyl-alpha-cyclodexrin (malphaCD)-catalyzed exchange of outer leaflet lipids (LEX) with 
      exogenous order- or disorder-promoting phospholipids. We examined the functional 
      impact of LEX by monitoring two Ag-stimulated responses: recruitment of 
      cytoplasmic Syk kinase to the inner leaflet and exocytosis of secretory granules 
      (degranulation). Based on the ImFCS data in resting cells, we observed global 
      increase or decrease of inner leaflet order when outer leaflet is exchanged with 
      order- or disorder-promoting lipids, respectively. We find that the degree of 
      both stimulated Syk recruitment and degranulation correlates positively with 
      LEX-mediated changes of inner leaflet order in resting cells. Overall, our 
      results show that resting-state lipid ordering of the outer leaflet influences 
      the ordering of the inner leaflet, likely via interleaflet coupling. This imposed 
      lipid reorganization modulates transmembrane signaling stimulated by Ag 
      clustering of IgE-FcepsilonRI.
CI  - Copyright (c) 2023 Biophysical Society. All rights reserved.
FAU - Yang, Gil-Suk
AU  - Yang GS
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New 
      York.
FAU - Wagenknecht-Wiesner, Alice
AU  - Wagenknecht-Wiesner A
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New 
      York.
FAU - Yin, Boyu
AU  - Yin B
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New 
      York.
FAU - Suresh, Pavana
AU  - Suresh P
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      New York.
FAU - London, Erwin
AU  - London E
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      New York.
FAU - Baird, Barbara A
AU  - Baird BA
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New 
      York.
FAU - Bag, Nirmalya
AU  - Bag N
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New 
      York; Department of Chemistry, Indian Institute of Technology, Kharagpur, India. 
      Electronic address: nirmalya@chem.iitkgp.ac.in.
LA  - eng
GR  - R35 GM122493/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20230801
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
SB  - IM
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2023/08/03 06:43
MHDA- 2023/08/03 06:43
CRDT- 2023/08/03 01:37
PHST- 2022/11/24 00:00 [received]
PHST- 2023/07/28 00:00 [revised]
PHST- 2023/07/31 00:00 [accepted]
PHST- 2023/08/03 06:43 [pubmed]
PHST- 2023/08/03 06:43 [medline]
PHST- 2023/08/03 01:37 [entrez]
AID - S0006-3495(23)00478-2 [pii]
AID - 10.1016/j.bpj.2023.07.027 [doi]
PST - aheadofprint
SO  - Biophys J. 2023 Aug 1:S0006-3495(23)00478-2. doi: 10.1016/j.bpj.2023.07.027.