PMID- 25153696
OWN - NLM
STAT- MEDLINE
DCOM- 20151112
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 8
DP  - 2014
TI  - Multiple regulatory roles of the mouse transmembrane adaptor protein NTAL in gene 
      transcription and mast cell physiology.
PG  - e105539
LID - 10.1371/journal.pone.0105539 [doi]
LID - e105539
AB  - Non-T cell activation linker (NTAL; also called LAB or LAT2) is a transmembrane 
      adaptor protein that is expressed in a subset of hematopoietic cells, including 
      mast cells. There are conflicting reports on the role of NTAL in the high 
      affinity immunoglobulin E receptor (FcepsilonRI) signaling. Studies carried out on mast 
      cells derived from mice with NTAL knock out (KO) and wild type mice suggested 
      that NTAL is a negative regulator of FcepsilonRI signaling, while experiments with 
      RNAi-mediated NTAL knockdown (KD) in human mast cells and rat basophilic leukemia 
      cells suggested its positive regulatory role. To determine whether different 
      methodologies of NTAL ablation (KO vs KD) have different physiological 
      consequences, we compared under well defined conditions FcepsilonRI-mediated signaling 
      events in mouse bone marrow-derived mast cells (BMMCs) with NTAL KO or KD. BMMCs 
      with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, 
      chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of 
      filamentous actin. These data provide clear evidence that NTAL is a negative 
      regulator of FcepsilonRI activation events in murine BMMCs, independently of possible 
      compensatory developmental alterations. To gain further insight into the role of 
      NTAL in mast cells, we examined the transcriptome profiles of resting and 
      antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this 
      analysis we identified several genes that were differentially regulated in 
      nonactivated and antigen-activated NTAL-deficient cells, when compared to the 
      corresponding control cells. Some of the genes seem to be involved in regulation 
      of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data 
      indicate multiple regulatory roles of NTAL in gene expression and mast cell 
      physiology.
FAU - Polakovicova, Iva
AU  - Polakovicova I
AD  - Department of Signal Transduction, Institute of Molecular Genetics, Academy of 
      Sciences of the Czech Republic, Prague, Czech Republic.
FAU - Draberova, Lubica
AU  - Draberova L
AD  - Department of Signal Transduction, Institute of Molecular Genetics, Academy of 
      Sciences of the Czech Republic, Prague, Czech Republic.
FAU - Simicek, Michal
AU  - Simicek M
AD  - Department of Signal Transduction, Institute of Molecular Genetics, Academy of 
      Sciences of the Czech Republic, Prague, Czech Republic.
FAU - Draber, Petr
AU  - Draber P
AD  - Department of Signal Transduction, Institute of Molecular Genetics, Academy of 
      Sciences of the Czech Republic, Prague, Czech Republic.
LA  - eng
SI  - GEO/GSE40731
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140825
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (LAB protein, mouse)
RN  - 0 (Receptors, IgE)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics/*metabolism
MH  - Animals
MH  - Calcium/metabolism
MH  - Mast Cells/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, IgE/*metabolism
MH  - Signal Transduction/immunology
MH  - Transcription, Genetic/*physiology
PMC - PMC4143283
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/08/26 06:00
MHDA- 2015/11/13 06:00
PMCR- 2014/08/25
CRDT- 2014/08/26 06:00
PHST- 2014/05/11 00:00 [received]
PHST- 2014/07/21 00:00 [accepted]
PHST- 2014/08/26 06:00 [entrez]
PHST- 2014/08/26 06:00 [pubmed]
PHST- 2015/11/13 06:00 [medline]
PHST- 2014/08/25 00:00 [pmc-release]
AID - PONE-D-14-21036 [pii]
AID - 10.1371/journal.pone.0105539 [doi]
PST - epublish
SO  - PLoS One. 2014 Aug 25;9(8):e105539. doi: 10.1371/journal.pone.0105539. 
      eCollection 2014.