PMID- 24292069
OWN - NLM
STAT- MEDLINE
DCOM- 20140210
LR  - 20211021
IS  - 1552-4469 (Electronic)
IS  - 1552-4450 (Linking)
VI  - 10
IP  - 1
DP  - 2014 Jan
TI  - Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine.
PG  - 61-8
LID - 10.1038/nchembio.1392 [doi]
AB  - Wnts are secreted palmitoylated glycoproteins that are important in embryonic 
      development and human cancers. Here we report a method for imaging the 
      palmitoylated form of Wnt proteins with subcellular resolution using clickable 
      bioorthogonal fatty acids and in situ proximity ligation. Palmitoylated Wnt3a is 
      visualized throughout the secretory pathway and trafficks to multivesicular 
      bodies that act as export sites in secretory cells. We establish that 
      glycosylation is not required for Wnt3a palmitoylation, which is necessary but 
      not sufficient for Wnt3a secretion. Wnt3a is palmitoylated by fatty acids 13-16 
      carbons in length at Ser209 but not at Cys77, consistent with a slow turnover 
      rate. We find that porcupine (PORCN) itself is palmitoylated, demonstrating what 
      is to our knowledge the first example of palmitoylation of an MBOAT protein, and 
      this modification partially regulates Wnt palmitoylation and signaling. Our data 
      reveal the role of O-palmitoylation in Wnt signaling and suggest another layer of 
      cellular control over PORCN function and Wnt secretion.
FAU - Gao, Xinxin
AU  - Gao X
AD  - Department of Early Discovery Biochemistry, Genentech, Inc., San Francisco, 
      California, USA.
FAU - Hannoush, Rami N
AU  - Hannoush RN
AD  - Department of Early Discovery Biochemistry, Genentech, Inc., San Francisco, 
      California, USA.
LA  - eng
PT  - Journal Article
DEP - 20131124
PL  - United States
TA  - Nat Chem Biol
JT  - Nature chemical biology
JID - 101231976
RN  - 0 (Membrane Proteins)
RN  - 0 (Palmitic Acids)
RN  - 0 (Wnt Proteins)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
SB  - IM
CIN - Nat Chem Biol. 2014 Jan;10(1):5-7. PMID: 24292072
MH  - Acyltransferases/*metabolism
MH  - Exosomes/metabolism
MH  - Glycosylation
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Palmitic Acids/*metabolism
MH  - Wnt Proteins/*metabolism
EDAT- 2013/12/03 06:00
MHDA- 2014/02/11 06:00
CRDT- 2013/12/03 06:00
PHST- 2013/04/21 00:00 [received]
PHST- 2013/10/17 00:00 [accepted]
PHST- 2013/12/03 06:00 [entrez]
PHST- 2013/12/03 06:00 [pubmed]
PHST- 2014/02/11 06:00 [medline]
AID - nchembio.1392 [pii]
AID - 10.1038/nchembio.1392 [doi]
PST - ppublish
SO  - Nat Chem Biol. 2014 Jan;10(1):61-8. doi: 10.1038/nchembio.1392. Epub 2013 Nov 24.