PMID- 27492485
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20210109
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 347
IP  - 1
DP  - 2016 Sep 10
TI  - Divergent effects of Porcupine and Wntless on WNT1 trafficking, secretion, and 
      signaling.
PG  - 171-183
LID - S0014-4827(16)30217-8 [pii]
LID - 10.1016/j.yexcr.2016.07.028 [doi]
AB  - Loss-of-function studies have identified Porcupine (PORCN) and Wntless (WLS) as 
      essential mediators of Wnt secretion and signaling. Whereas PORCN is thought to 
      palmitoylate Wnt proteins, WLS is believed to transport palmitoylated Wnt 
      proteins to the cell surface. However, little is known about how these two 
      proteins cooperate to regulate Wnt palmitoylation, trafficking, secretion, and 
      signaling. We first investigated possible interactions between PORCN, WLS, and 
      WNT1, by carrying out co-immunoprecipitation studies. These studies demonstrate 
      the existence of a complex containing PORCN and WLS. They further show that PORCN 
      and WLS compete for binding to WNT1. Then, we used gain-of-function studies to 
      investigate the cooperation between PORCN and WLS as well as possible biochemical 
      interactions between PORCN, WLS, and WNT1. Consistent with the proposed roles for 
      PORCN and WLS, we show that overexpression of PORCN promotes palmitoylation of 
      WNT1 while overexpression of WLS does not. Overexpression of PORCN enhances the 
      ability of WLS to promote WNT1 trafficking to the cell surface as well as 
      secretion, but decreases the ability of WLS to activate WNT1 signaling in target 
      cell. These observations suggest that the levels of WNT1 on the cell surface and 
      in the media are not the sole determinants of the activation of Wnt signaling in 
      target cells.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Galli, Lisa M
AU  - Galli LM
AD  - Department of Biology, San Francisco State University, 1600 Holloway Avenue, San 
      Francisco, CA 94132, USA.
FAU - Zebarjadi, Navid
AU  - Zebarjadi N
AD  - Department of Biology, San Francisco State University, 1600 Holloway Avenue, San 
      Francisco, CA 94132, USA.
FAU - Li, Lydia
AU  - Li L
AD  - Department of Biology, San Francisco State University, 1600 Holloway Avenue, San 
      Francisco, CA 94132, USA.
FAU - Lingappa, Vishwanath R
AU  - Lingappa VR
AD  - Prosetta Biosciences, Inc., 670 5th Street, San Francisco, CA 94107, USA.
FAU - Burrus, Laura W
AU  - Burrus LW
AD  - Department of Biology, San Francisco State University, 1600 Holloway Avenue, San 
      Francisco, CA 94132, USA. Electronic address: LBurrus@sfsu.edu.
LA  - eng
GR  - P20 MD000262/MD/NIMHD NIH HHS/United States
GR  - R15 HD070206/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20160801
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Wnt1 Protein)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (Porcn protein, mouse)
SB  - IM
MH  - Acyltransferases
MH  - Animals
MH  - Autocrine Communication/drug effects
MH  - COS Cells
MH  - Chickens
MH  - Chlorocebus aethiops
MH  - HEK293 Cells
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Lipoylation/drug effects
MH  - Membrane Microdomains/drug effects/metabolism
MH  - Membrane Proteins/*metabolism
MH  - Paracrine Communication/drug effects
MH  - Protein Binding/drug effects
MH  - Protein Transport/drug effects
MH  - *Wnt Signaling Pathway
MH  - Wnt1 Protein/*metabolism
PMC - PMC5032901
MID - NIHMS809341
OTO - NOTNLM
OT  - Palmitoylation
OT  - Porcupine
OT  - Secretion
OT  - WNT1
OT  - Wntless
OT  - beta-catenin dependent signaling
EDAT- 2016/08/06 06:00
MHDA- 2017/05/16 06:00
PMCR- 2017/09/10
CRDT- 2016/08/06 06:00
PHST- 2016/03/23 00:00 [received]
PHST- 2016/07/12 00:00 [revised]
PHST- 2016/07/31 00:00 [accepted]
PHST- 2016/08/06 06:00 [entrez]
PHST- 2016/08/06 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2017/09/10 00:00 [pmc-release]
AID - S0014-4827(16)30217-8 [pii]
AID - 10.1016/j.yexcr.2016.07.028 [doi]
PST - ppublish
SO  - Exp Cell Res. 2016 Sep 10;347(1):171-183. doi: 10.1016/j.yexcr.2016.07.028. Epub 
      2016 Aug 1.