Related Experiment Video

Updated: Jan 12, 2026

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
13:45

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin

Published on: December 23, 2010

13.2K

B4GALT1 and Wntless collaborate to block LRP5/6 translocation from Golgi to cell surface

Xinyang Li1, Yue Hua2, Jiahui Wang1

  • 1Department of Biochemistry and Molecular Biology, Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.

The Journal of Cell Biology
|November 3, 2025
PubMed

Insights

The Golgi enzyme B4GALT1 retains co-receptors LRP5/6 in the Golgi, reducing their cell surface presence. Wnt secretion activity counteracts this retention, influencing LRP5/6 cell surface presentation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Low-density lipoprotein receptor-related protein 5/6 (LRP5/6) are crucial co-receptors for Wnt proteins, mediating WNT/β-catenin signaling.
  • LRP5/6 are transported through the endoplasmic reticulum and Golgi apparatus to the cell surface after translation.

Purpose of the Study:

  • To investigate the role of Golgi-resident β-1, 4-galactosyltransferase (B4GALT1) in the trafficking and cell surface presentation of LRP5/6.
  • To elucidate the interplay between B4GALT1, LRP5/6, and Wnt secretion in regulating WNT/β-catenin signaling.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Cell surface protein biotinylation and Western blotting to quantify cell surface LRP5/6 levels.
  • Treatment with LGK974 to disrupt the Wnt/Wntless complex.

Main Results:

  • B4GALT1 directly interacts with LRP5/6, leading to their retention in the Golgi apparatus and reduced cell surface expression.
  • B4GALT1 also binds to Wntless, a Wnt transporter, but this interaction modulates LRP5/6 Golgi retention rather than affecting Wnt secretion.
  • Wnt secretion, by occupying Wntless, antagonizes B4GALT1-mediated LRP5/6 Golgi retention.
  • Inhibition of the Wnt/Wntless complex using LGK974 enhances LRP5/6 Golgi retention, decreasing their translocation to the cell surface.

Conclusions:

  • The cell surface presentation of LRP5/6 is dynamically regulated by the Golgi-resident enzyme B4GALT1.
  • Wnt secretion activity plays a significant role in counteracting B4GALT1-mediated LRP5/6 retention, thereby influencing LRP5/6 availability at the cell surface.

More Related Videos

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells11:05

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

9.6K
Modeling Paracrine Noncanonical Wnt Signaling In Vitro11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

1.9K

Related Concept Videos

Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
3.5K
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.2K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.9K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.9K