Arginine methylation is required for canonical Wnt signaling and endolysosomal trafficking

Proceedings of the National Academy of Sciences of the United States of America
Lauren V AlbrechtEdward M De Robertis

Abstract

Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications. Intriguingly, a cytoskeletal protein was previously known to have meArg modifications that enhanced subsequent phosphorylations by GSK3. Here, we report the unexpected finding that protein arginine methyltransferase 1 (PRMT1) is required for canonical Wnt signaling. Treatment of cultured cells for 5-30 min with Wnt3a induced a large increase in total endocytic vesicles which were also positive for asymmetric dimethylarginine modifications. Protease protection studies, both biochemical and in situ in cultured cells, showed that many meArg-modified cytosolic proteins became rapidly translocated into MVBs together with GSK3 and Lys48-polyubiquitinated proteins...Continue Reading

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Citations

Sep 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yi DingEdward M De Robertis
May 8, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nydia Tejeda-MuñozEdward M De Robertis
Feb 28, 2020·EMBO Reports·Dong-Seok ParkSun-Cheol Choi
Mar 20, 2020·EMBO Reports·Peter Ten Dijke, David Baker
May 19, 2019·Cellular and Molecular Life Sciences : CMLS·Benjamin M Lorton, David Shechter
Jul 3, 2020·Development·Karen LinnemannstönsJulia Christina Gross
Aug 11, 2020·Cell Communication and Signaling : CCS·Xueqiang PengHangyu Li
Jan 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lauren V AlbrechtEdward M De Robertis
Sep 10, 2019·Frontiers in Immunology·Tanushree Mukherjee, Kithiganahalli Narayanaswamy Balaji
Sep 3, 2020·Cancer Research·Oleg TimofeevUNKNOWN German Mouse Clinic Consortium
Dec 31, 2020·STAR Protocols·L V AlbrechtE M De Robertis
Jul 9, 2020·Data in Brief·Dimitris KyriakouAntonis Kirmizis
Dec 15, 2020·Frontiers in Oncology·Bárbara Paranhos CoelhoMarilene Hohmuth Lopes
Feb 24, 2021·Development, Growth & Differentiation·Gabriele Colozza, Bon-Kyoung Koo
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Jul 2, 2021·Annual Review of Cell and Developmental Biology·Lauren V AlbrechtEdward M De Robertis

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Methods Mentioned

BETA
phase contrast microscopy
transfection
flow cytometry
immunoprecipitations
PCR
light microscopy

Software Mentioned

ImageJ
ImageJ NIH
MaxEntropy
CellQuest
FIJI ImageJ
Zeiss

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