A Wntless-SEC12 complex on the ER membrane regulates early Wnt secretory vesicle assembly and mature ligand export.

Journal of Cell Science
Jiaxin SunNan Gao

Abstract

Wntless (Wls) transports Wnt molecules for secretion; however, the cellular mechanism underlying the initial assembly of Wnt secretory vesicles is still not fully defined. Here, we performed proteomic and mutagenic analyses of mammalian Wls, and report a mechanism for formation of early Wnt secretory vesicles on ER membrane. Wls forms a complex with SEC12 (also known as PREB), an ER membrane-localized guanine nucleotide-exchange factor (GEF) activator of the SAR1 (the SAR1A isoform) small GTPase. Compared to palmitoylation-deficient Wnt molecules, binding of mature Wnt to Wls increases Wls-SEC12 interaction and promotes association of Wls with SAR1, the key activator of the COPII machinery. Incorporation of Wls into this exporting ER compartment is affected by Wnt ligand binding and SEC12 binding to Wls, as well as the structural integrity and, potentially, the folding of the cytosolic tail of Wls. In contrast, Wls-SEC12 binding is stable, with the interacting interface biochemically mapped to cytosolic segments of individual proteins. Mutant Wls that fails to communicate with the COPII machinery cannot effectively support Wnt secretion. These data suggest that formation of early Wnt secretory vesicles is carefully regulated to...Continue Reading

References

May 16, 1998·The Journal of Cell Biology·M AridorW E Balch
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·P A SkehelE R Kandel
Jun 5, 2001·Nature Cell Biology·B AntonnyR Schekman
Jan 25, 2005·Nature Structural & Molecular Biology·Ken Sato, Akihiko Nakano
Jan 25, 2006·Current Biology : CB·Rebecca ForsterRainer Pepperkok
May 9, 2006·Cell·Kerstin BartschererMichael Boutros
Nov 17, 2006·Development·Robyn M GoodmanErica M Selva
Nov 23, 2006·The Biochemical Journal·Manabu KurayoshiAkira Kikuchi
Dec 5, 2006·Developmental Cell·Ritsuko TakadaShinji Takada
Dec 28, 2007·Developmental Cell·Chun-Liang PanGian Garriga
Dec 28, 2007·Developmental Cell·Pei-Tzu YangHendrik C Korswagen
Jan 15, 2008·Nature Cell Biology·Fillip PortKonrad Basler
Jan 15, 2008·Nature Cell Biology·Xavier Franch-MarroJean-Paul Vincent
Nov 5, 2008·The Journal of Cell Biology·Raul RojasJuan S Bonifacino
Jul 22, 2009·Developmental Cell·Bryan T MacDonaldXi He
Jul 30, 2009·Journal of Cell Science·Helen HughesDavid J Stephens
Oct 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jiang FuWei Hsu
May 11, 2010·Trends in Biochemical Sciences·Christian U StirnimannChristoph W Müller
May 12, 2010·Biochemical and Biophysical Research Communications·Xiaolei ZhuangKausik Ray
Sep 10, 2010·Journal of Cell Science·Gary S CoombsDavid M Virshup
Nov 19, 2011·EMBO Reports·Tina BuechlingMichael Boutros
Nov 24, 2011·Developmental Biology·Patrick Herr, Konrad Basler
Feb 22, 2012·PloS One·Elisabeth A MontegnaBenjamin S Glick
Feb 23, 2012·The Journal of Clinical Investigation·Ryotaro SakamoriNan Gao
Feb 24, 2012·Nature·Lingyan JinMichael Rape
Jun 2, 2012·Science·Claudia Y JandaK Christopher Garcia
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse

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