PMID- 38201297
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240201
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 13
IP  - 1
DP  - 2024 Jan 1
TI  - The Underlying Rab Network of MRGPRX2-Stimulated Secretion Unveils the Impact of 
      Receptor Trafficking on Secretory Granule Biogenesis and Secretion.
LID - 10.3390/cells13010093 [doi]
LID - 93
AB  - MRGPRX2, the human member of the MAS-related G-protein-coupled receptors (GPCRs), 
      mediates the immunoglobulin E (IgE)-independent responses of a subset of mast 
      cells (MCs) that are associated with itch, pain, neurogenic inflammation, and 
      pseudoallergy to drugs. The mechanisms underlying the responses of MRGPRX2 to its 
      multiple and diverse ligands are still not completely understood. Given the close 
      association between GPCR location and function, and the key role played by Rab 
      GTPases in controlling discrete steps along vesicular trafficking, we aimed to 
      reveal the vesicular pathways that directly impact MRGPRX2-mediated exocytosis by 
      identifying the Rabs that influence this process. For this purpose, we screened 
      43 Rabs for their functional and phenotypic impacts on MC degranulation in 
      response to the synthetic MRGPRX2 ligand compound 48/80 (c48/80), which is often 
      used as the gold standard of MRGPRX2 ligands, or to substance P (SP), an 
      important trigger of neuroinflammatory MC responses. Results of this study 
      highlight the important roles played by macropinocytosis and autophagy in 
      controlling MRGPRX2-mediated exocytosis, demonstrating a close feedback control 
      between the internalization and post-endocytic trafficking of MRGPRX2 and its 
      triggered exocytosis.
FAU - Lazki-Hagenbach, Pia
AU  - Lazki-Hagenbach P
AUID- ORCID: 0000-0003-0521-7981
AD  - Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv 
      University, Tel Aviv 69978, Israel.
FAU - Kleeblatt, Elisabeth
AU  - Kleeblatt E
AD  - Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv 
      University, Tel Aviv 69978, Israel.
FAU - Fukuda, Mitsunori
AU  - Fukuda M
AUID- ORCID: 0000-0002-8620-5853
AD  - Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life 
      Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, 
      Sendai 980-8578, Miyagi, Japan.
FAU - Ali, Hydar
AU  - Ali H
AUID- ORCID: 0000-0001-9190-1960
AD  - Department of Basic and Translational Sciences, School of Dental Medicine, 
      University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Sagi-Eisenberg, Ronit
AU  - Sagi-Eisenberg R
AUID- ORCID: 0000-0002-1990-8831
AD  - Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv 
      University, Tel Aviv 69978, Israel.
AD  - Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel.
LA  - eng
GR  - 2021172/United States-Israel Binational Science Foundation/
GR  - 1600/19/Israel Science Foundation/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240101
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (MRGPRX2 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Neuropeptide)
RN  - 0 (Receptors, G-Protein-Coupled)
SB  - IM
MH  - Humans
MH  - *Bodily Secretions
MH  - *Exocytosis
MH  - Autophagy
MH  - Immunoglobulin E
MH  - Inflammation
MH  - Secretory Vesicles
MH  - Nerve Tissue Proteins
MH  - Receptors, Neuropeptide
MH  - Receptors, G-Protein-Coupled
PMC - PMC10778293
OTO - NOTNLM
OT  - MAS-related G-protein-coupled receptors
OT  - MRGPRX2
OT  - RBL-2H3
OT  - Rab GTPase
OT  - degranulation
OT  - mast cells
COIS- The authors declare no conflicts of interest.
EDAT- 2024/01/11 07:42
MHDA- 2024/01/12 06:43
PMCR- 2024/01/01
CRDT- 2024/01/11 01:04
PHST- 2023/12/02 00:00 [received]
PHST- 2023/12/18 00:00 [revised]
PHST- 2023/12/28 00:00 [accepted]
PHST- 2024/01/12 06:43 [medline]
PHST- 2024/01/11 07:42 [pubmed]
PHST- 2024/01/11 01:04 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - cells13010093 [pii]
AID - cells-13-00093 [pii]
AID - 10.3390/cells13010093 [doi]
PST - epublish
SO  - Cells. 2024 Jan 1;13(1):93. doi: 10.3390/cells13010093.