PMID- 23171960
OWN - NLM
STAT- MEDLINE
DCOM- 20130529
LR  - 20211203
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Print)
IS  - 1015-8987 (Linking)
VI  - 30
IP  - 6
DP  - 2012
TI  - SGK3 regulates Ca(2+) entry and migration of dendritic cells.
PG  - 1423-35
LID - 10.1159/000343330 [doi]
AB  - BACKGROUND/AIMS: Dendritic cells (DCs) are antigen-presenting cells linking 
      innate and adaptive immunity. DC maturation and migration are governed by 
      alterations of cytosolic Ca(2+) concentrations ([Ca(2+)](i)). Ca(2+) entry is in 
      part accomplished by store-operated Ca(2+) (SOC) channels consisting of the 
      membrane pore-forming subunit Orai and the ER Ca(2+) sensing subunit STIM. 
      Moreover, DC functions are under powerful regulation of the 
      phosphatidylinositol-3-kinase (PI3K) pathway, which suppresses proinflammatory 
      cytokine production but supports DC migration. Downstream targets of PI3K include 
      serum- and glucocorticoid-inducible kinase isoform SGK3. The present study 
      explored, whether SGK3 participates in the regulation of [Ca(2+)](i) and 
      Ca(2+)-dependent functions of DCs, such as maturation and migration. 
      METHODS/RESULTS: Experiments were performed with bone marrow derived DCs from 
      gene targeted mice lacking SGK3 (sgk3(-/-)) and DCs from their wild type 
      littermates (sgk3(+/+)). Maturation, phagocytosis and cytokine production were 
      similar in sgk3(-/-) and sgk3(+/+) DCs. However, SOC entry triggered by 
      intracellular Ca(2+) store depletion with the endosomal Ca(2+) ATPase inhibitor 
      thapsigargin (1 microM) was significantly reduced in sgk3(-/-) compared to sgk3(+/+) 
      DCs. Similarly, bacterial lipopolysaccharide (LPS, 1 microg/ml)- and chemokine CXCL12 
      (300 ng/ml)- induced increase in [Ca(2+)](i) was impaired in sgk3(-/-) DCs. 
      Moreover, currents through SOC channels were reduced in sgk3(-/-) DCs. STIM2 
      transcript levels and protein abundance were significantly lower in sgk3(-/-) DCs 
      than in sgk3(+/+) DCs, whereas Orai1, Orai2, STIM1 and TRPC1 transcript levels 
      and/or protein abundance were similar in sgk3-/- and sgk3(+/+) DCs. Migration of 
      both, immature DCs towards CXCL12 and LPS-matured DCs towards CCL21 was reduced 
      in sgk3(-/-) as compared to sgk3(+/+) DCs. Migration of sgk3(+/+) DCs was further 
      sensitive to SOC channel inhibitor 2-APB (50 microM) and to STIM1/STIM2 knock-down. 
      CONCLUSION: SGK3 contributes to the regulation of store-operated Ca(2+) entry 
      into and migration of dendritic cells, effects at least partially mediated 
      through SGK3-dependent upregulation of STIM2 expression.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Schmid, Evi
AU  - Schmid E
AD  - Department of Physiology, University of Tubingen, Tubingen, Germany.
FAU - Bhandaru, Madhuri
AU  - Bhandaru M
FAU - Nurbaeva, Meerim K
AU  - Nurbaeva MK
FAU - Yang, Wenting
AU  - Yang W
FAU - Szteyn, Kalina
AU  - Szteyn K
FAU - Russo, Antonella
AU  - Russo A
FAU - Leibrock, Christina
AU  - Leibrock C
FAU - Tyan, Leonid
AU  - Tyan L
FAU - Pearce, David
AU  - Pearce D
FAU - Shumilina, Ekaterina
AU  - Shumilina E
FAU - Lang, Florian
AU  - Lang F
LA  - eng
GR  - R01 DK056695/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20121122
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Calcium Channels)
RN  - 0 (Cytokines)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Sgk3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Calcium Channels/genetics/metabolism
MH  - *Calcium Signaling
MH  - *Cell Movement
MH  - Cells, Cultured
MH  - Cytokines/physiology
MH  - Dendritic Cells/*enzymology/physiology
MH  - Female
MH  - Gene Expression
MH  - Male
MH  - Membrane Potentials
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Patch-Clamp Techniques
MH  - Phagocytosis
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism/physiology
PMC - PMC6175581
MID - NIHMS990696
EDAT- 2012/11/23 06:00
MHDA- 2013/05/31 06:00
PMCR- 2018/10/08
CRDT- 2012/11/23 06:00
PHST- 2012/10/29 00:00 [accepted]
PHST- 2012/11/23 06:00 [entrez]
PHST- 2012/11/23 06:00 [pubmed]
PHST- 2013/05/31 06:00 [medline]
PHST- 2018/10/08 00:00 [pmc-release]
AID - 000343330 [pii]
AID - 10.1159/000343330 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2012;30(6):1423-35. doi: 10.1159/000343330. Epub 2012 Nov 
      22.