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Commun Biol. 2018 Oct 10;1:165. doi: 10.1038/s42003-018-0172-x. eCollection 2018.

Assembly of protein complexes restricts diffusion of Wnt3a proteins.

Author information

1
1Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 Japan.
2
2National Institute for Basic Biology, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 Japan.
3
3The Graduate University for Advanced Studies (SOKENDAI), 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 Japan.
4
U-Medico Inc., 2-1 Yamadaoka, Suita, Osaka 565-0871 Japan.
5
5Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 Japan.
6
6Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 Japan.
7
7Molecular Profiling Research Center for Drug Discovery and OPERANDO Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), 2-3-26 Aomi, Koto-ku, Tokyo 135-0064 Japan.
8
8Field Solution Division, JEOL Ltd., 1156 Nakagami, Akishima, Tokyo 196-0022 Japan.
9
BioNet Laboratory Inc., 2-3-28 Nishiki-chou, Tachikawa, Tokyo 190-0022 Japan.
10
Cluster for Pioneering Research, Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan.
11
11Asan Institute for Life Sciences, Asan Medical Center & University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul 05505 Republic of Korea.

Abstract

Members of the Wnt protein family play roles in many aspects of embryogenesis and homeostasis. Despite their biological significance, characteristics of Wnt proteins still remain unclear, mainly due to their insolubility after the removal of serum. Here we examine Wnt proteins in serum-containing media by using analytical ultracentrifugation with a fluorescence detection system. This analysis reveals that Wnt3a assembles into high-molecular-weight complexes that become dissociable by interaction with the extracellular domain of the Frizzled8 receptor or secreted Wnt-binding protein sFRP2. Cross-linking and single-particle analyses of Wnt3a fractionated by gel filtration chromatography show the homo-trimer to be the smallest form of the assembled Wnt3a complexes. Fluorescence correlation spectroscopy and immunohistochemistry reveal that the assembly of Wnt3a complexes restricted their diffusion and signaling range in Xenopus laevis embryos. Thus, we propose that the Wnt diffusion range can be controlled by a balance between the assembly of Wnt complexes and their dissociation.

Conflict of interest statement

The authors declare no competing interests.

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