PMID- 23350699
OWN - NLM
STAT- MEDLINE
DCOM- 20140904
LR  - 20211021
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 33
IP  - 2
DP  - 2013 Mar 7
TI  - ALG-2-interacting Tubby-like protein superfamily member PLSCR3 is secreted by an 
      exosomal pathway and taken up by recipient cultured cells.
PG  - e00026
LID - 10.1042/BSR20120123 [doi]
LID - e00026
AB  - PLSCRs (phospholipid scramblases) are palmitoylated membrane-associating 
      proteins. Regardless of the given names, their physiological functions are not 
      clear and thought to be unrelated to phospholipid scrambling activities observed 
      in vitro. Using a previously established cell line of HEK-293 (human embryonic 
      kidney-293) cells constitutively expressing human Scr3 (PLSCR3) that interacts 
      with ALG-2 (apoptosis-linked gene 2) Ca(2)(+)-dependently, we found that Scr3 was 
      secreted into the culture medium. Secretion of Scr3 was suppressed by 2-BP 
      (2-bromopalmitate, a palmitoylation inhibitor) and by GW4869 (an inhibitor of 
      ceramide synthesis). Secreted Scr3 was recovered in exosomal fractions by sucrose 
      density gradient centrifugation. Palmitoylation sites and the N-terminal Pro-rich 
      region were necessary for efficient secretion, but ABSs (ALG-2-binding sites) 
      were dispensable. Overexpression of GFP (green fluorescent protein)-fused 
      VPS4B(E235Q), a dominant negative mutant of an AAA (ATPase associated with 
      various cellular activities) ATPase with a defect in disassembling ESCRT 
      (endosomal sorting complex required for transport)-III subunits, significantly 
      reduced secretion of Scr3. Immunofluorescence microscopic analyses showed that 
      Scr3 was largely localized to enlarged endosomes induced by overexpression of a 
      GFP-fused constitutive active mutant of Rab5A (GFP-Rab5A(Q79L)). Secreted Scr3 
      was taken up by HeLa cells, suggesting that Scr3 functions as a cell-to-cell 
      transferable modulator carried by exosomes in a paracrine manner.
FAU - Inuzuka, Tatsutoshi
AU  - Inuzuka T
AD  - *Department of Applied Molecular Biosciences, Graduate School of Bioagricultural 
      Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Inokawa, Akira
AU  - Inokawa A
AD  - *Department of Applied Molecular Biosciences, Graduate School of Bioagricultural 
      Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Chen, Cen
AU  - Chen C
AD  - *Department of Applied Molecular Biosciences, Graduate School of Bioagricultural 
      Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Kizu, Kumiko
AU  - Kizu K
AD  - daggerDepartment of Food and Nutrition, Kyoto Women's University, 35 Kitahiyoshi-cho, 
      Imakumano, Higashiyama-ku, Kyoto 605-8501, Japan.
FAU - Narita, Hiroshi
AU  - Narita H
AD  - daggerDepartment of Food and Nutrition, Kyoto Women's University, 35 Kitahiyoshi-cho, 
      Imakumano, Higashiyama-ku, Kyoto 605-8501, Japan.
FAU - Shibata, Hideki
AU  - Shibata H
AD  - *Department of Applied Molecular Biosciences, Graduate School of Bioagricultural 
      Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Maki, Masatoshi
AU  - Maki M
AD  - *Department of Applied Molecular Biosciences, Graduate School of Bioagricultural 
      Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130307
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (PDCD6 protein, human)
RN  - 0 (PLSCR3 protein, human)
RN  - 0 (Palmitates)
RN  - 0 (Phospholipid Transfer Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 18263-25-7 (2-bromopalmitate)
SB  - IM
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - Binding Sites
MH  - Biological Transport/*genetics
MH  - Calcium-Binding Proteins/*metabolism
MH  - Cells, Cultured
MH  - Exosomes/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Green Fluorescent Proteins
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Lipoylation/*drug effects
MH  - Palmitates/pharmacology
MH  - Phospholipid Transfer Proteins/genetics/*metabolism
MH  - Protein Binding
MH  - Signal Transduction/drug effects
PMC - PMC3590573
EDAT- 2013/01/29 06:00
MHDA- 2014/09/05 06:00
PMCR- 2013/03/07
CRDT- 2013/01/29 06:00
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2014/09/05 06:00 [medline]
PHST- 2013/03/07 00:00 [pmc-release]
AID - BSR20120123 [pii]
AID - 10.1042/BSR20120123 [doi]
PST - epublish
SO  - Biosci Rep. 2013 Mar 7;33(2):e00026. doi: 10.1042/BSR20120123.