PMID- 30327201
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20231213
IS  - 1879-2596 (Electronic)
IS  - 0167-4889 (Linking)
VI  - 1865
IP  - 11 Pt A
DP  - 2018 Nov
TI  - Anoctamin-6 regulates ADAM sheddase function.
PG  - 1598-1610
LID - S0167-4889(18)30287-8 [pii]
LID - 10.1016/j.bbamcr.2018.08.011 [doi]
AB  - ADAM17, a prominent member of the "Disintegrin and Metalloproteinase" (ADAM) 
      family, controls vital cellular functions through cleavage of transmembrane 
      substrates including TGF-alpha, Amphiregulin (AREG) and TNF-Receptor 1 (TNFR1). 
      We recently presented evidence that surface exposure of phosphatidylserine (PS) 
      is pivotal for ADAM17 to exert sheddase activity. Anoctamin-6 (ANO6) has 
      Ca(2+)-dependent phospholipid scramblase activity and it followed that the 
      functions of ANO6 and ADAM17 might be linked. We report that overexpression of 
      ANO6 in HEK293T cells led to increased Ca(2+)-mediated PS-exposure that was 
      indeed accompanied by enhanced release of AREG and TGF-alpha. The effect was not 
      observed when cells were treated with the PKC-dependent ADAM17 activator PMA. 
      Transformation of cells with a constitutively active ANO6 mutant led to 
      spontaneous PS-exposure and to the release of ADAM17-substrates in the absence of 
      any stimuli. Inhibitor experiments indicated that ANO6-mediated enhancement of 
      substrate cleavage simultaneously broadened the spectrum of participating 
      metalloproteinases. In complementary experiments, siRNA-mediated downregulation 
      of ANO6 was shown to decrease ionophore-mediated release of TNFR1 in human 
      umbilical vein endothelial cells (HUVECs). We conclude that ANO6, by virtue of 
      its scramblase activity, may play a role as an important regulator of the 
      ADAM-network in the plasma membrane.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Veit, Martin
AU  - Veit M
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Koyro, Katharina Isabelle
AU  - Koyro KI
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Ahrens, Bjorn
AU  - Ahrens B
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Bleibaum, Florian
AU  - Bleibaum F
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Munz, Martin
AU  - Munz M
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Rovekamp, Hagen
AU  - Rovekamp H
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Andra, Jorg
AU  - Andra J
AD  - Hamburg University of Applied Science, Ulmenliet 20, 21033 Hamburg, Germany.
FAU - Schreiber, Rainer
AU  - Schreiber R
AD  - Physiological Institute, University of Regensburg, Universitatsstrasse 31, 93053 
      Regensburg, Germany.
FAU - Kunzelmann, Karl
AU  - Kunzelmann K
AD  - Physiological Institute, University of Regensburg, Universitatsstrasse 31, 93053 
      Regensburg, Germany.
FAU - Sommer, Anselm
AU  - Sommer A
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Bhakdi, Sucharit
AU  - Bhakdi S
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany.
FAU - Reiss, Karina
AU  - Reiss K
AD  - Dept. of Dermatology, University of Kiel, 24105 Kiel, Germany. Electronic 
      address: kreiss@dermatology.uni-kiel.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180823
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Res
JT  - Biochimica et biophysica acta. Molecular cell research
JID - 101731731
RN  - 0 (ANO6 protein, human)
RN  - 0 (Anoctamins)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Phospholipid Transfer Proteins)
RN  - 0 (Phospholipids)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 56092-81-0 (Ionomycin)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - ADAM Proteins/*metabolism
MH  - ADAM17 Protein/metabolism
MH  - Anoctamins/*metabolism
MH  - Calcium/metabolism
MH  - Cell Membrane/metabolism
MH  - Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Ionomycin/pharmacology
MH  - Models, Biological
MH  - Mutation
MH  - Phosphatidylserines/*metabolism
MH  - Phospholipid Transfer Proteins/*metabolism
MH  - Phospholipids/*metabolism
MH  - Transforming Growth Factor alpha/metabolism
OTO - NOTNLM
OT  - ADAM17
OT  - Anoctamin-6
OT  - Phosphatidylserine
OT  - Scramblase
OT  - Shedding
EDAT- 2018/10/18 06:00
MHDA- 2019/05/22 06:00
CRDT- 2018/10/18 06:00
PHST- 2018/04/13 00:00 [received]
PHST- 2018/08/17 00:00 [revised]
PHST- 2018/08/20 00:00 [accepted]
PHST- 2018/10/18 06:00 [entrez]
PHST- 2018/10/18 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
AID - S0167-4889(18)30287-8 [pii]
AID - 10.1016/j.bbamcr.2018.08.011 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 Pt A):1598-1610. doi: 
      10.1016/j.bbamcr.2018.08.011. Epub 2018 Aug 23.