Last update 01 Nov 2024

WLS

Last update 01 Nov 2024

Basic Info

Synonyms

C1orf139, EVI, FLJ23091

+ [9]

Introduction

Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins (PubMed:34587386). Plays also an important role in establishment of the anterior-posterior body axis formation during development (By similarity).

Drugs associated with WLS

YW-1128

Target

CTNNB1 x WLS

Mechanism

CTNNB1 inhibitors [+1]

Active Org.

Guangzhou Medical University [+1]

Originator Org.

University of Maryland

Active Indication

Carbohydrate Metabolism, Inborn Errors [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NOV-1502

Target

CTNNB1 x RAS x WLS

Mechanism

CTNNB1 modulators [+2]

Active Org.

Yonsei University

Originator Org.

Yonsei University

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

P-975

Target

WLS

Mechanism

WLS gene modulators

Active Org.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Originator Org.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Active Indication

Brain Cancer

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with WLS

100 Translational Medicine associated with WLS

0 Patents (Medical) associated with WLS

290

Literatures (Medical) associated with WLS

01 Oct 2024·PROTEOMICS

The temporal protein signature analyses of developing human deciduous molar tooth germ

Article

Author: Wu, Buling ; Xiong, Fu ; Hu, Liang ; Zhang, Jian ; Chen, Xiaohang ; Wei, Fengxiang ; Zhao, Guoqiang ; Li, Gaochi

AbstractThe tooth serves as an exemplary model for developmental studies, encompassing epithelial‐mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time‐dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap‐to‐early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co‐expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single‐cell RNA‐sequencing (scRNA‐seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

01 Sep 2024·Traffic

Dissociation of Drosophila Evi‐Wg Complex Occurs Post Apical Internalization in the Maturing Acidic Endosomes

Article

Author: Sharma, Satyam ; Chaudhary, Varun

ABSTRACTSignaling pathways activated by secreted Wnt ligands play an essential role in tissue development and the progression of diseases, like cancer. Secretion of the lipid‐modified Wnt proteins is tightly regulated by a repertoire of intracellular factors. For instance, a membrane protein, Evi, interacts with the Wnt ligand in the ER, and it is essential for its further trafficking and release in the extracellular space. After dissociating from the Wnt, the Wnt‐unbound Evi is recycled back to the ER via Golgi. However, where in this trafficking path Wnt proteins dissociate from Evi remains unclear. Here, we have used the Drosophila wing epithelium to trace the route of the Evi‐Wg (Wnt homolog) complex leading up to their separation. In these polarized cells, Wg is first trafficked to the apical surface; however, the secretion of Wg is believed to occurs post‐internalization via recycling. Our results show that the Evi‐Wg complex is internalized from the apical surface and transported to the retromer‐positive endosomes. Furthermore, using antibodies that specifically label the Wnt‐unbound Evi, we show that Evi and Wg separation occurs post‐internalization in the acidic endosomes. These results refine our understanding of the polarized trafficking of Wg and highlight the importance of Wg endocytosis in its secondary secretion.

01 Sep 2024·Autophagy

The Wolfram-like variant WFS1 ^E864K destabilizes MAM and compromises autophagy and mitophagy in human and mice

Article

Author: Bataillard, Méghane S. ; Tranebjærg, Lisbeth ; Richard, Elodie M. ; Delprat, Benjamin ; Patergnani, Simone ; Maurice, Tangui ; Cazevieille, Chantal ; Valéro, René ; Pinton, Paolo ; Alves, Stacy ; Danese, Alberto

Dominant variants in WFS1 (wolframin ER transmembrane glycoprotein), the gene coding for a mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein, have been associated with Wolfram-like syndrome (WLS). In vitro and in vivo, WFS1 loss results in reduced ER to mitochondria calcium (Ca²⁺) transfer, mitochondrial dysfunction, and enhanced macroautophagy/autophagy and mitophagy. However, in the WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown. Here, we show that in human fibroblasts and murine neuronal cultures the WLS protein WFS1^E864K leads to decreases in mitochondria bioenergetics and Ca²⁺ uptake, deregulation of the mitochondrial quality system mechanisms, and alteration of the autophagic flux. Moreover, in the Wfs1^E864K mouse, these alterations are concomitant with a decrease of MAM number. These findings reveal pathophysiological similarities between WS and WLS, highlighting the importance of WFS1 for MAM's integrity and functionality. It may open new treatment perspectives for patients with WLS.Abbreviations: BafA1: bafilomycin A₁; ER: endoplasmic reticulum; HSPA9/GRP75: heat shock protein family A (Hsp70) member 9; ITPR/IP₃R: inositol 1,4,5-trisphosphate receptor; MAM: mitochondria-associated endoplasmic reticulum membrane; MCU: mitochondrial calcium uniporter; MFN2: mitofusin 2; OCR: oxygen consumption rate; ROS: reactive oxygen species; ROT/AA: rotenone+antimycin A; VDAC1: voltage dependent anion channel 1; WLS: Wolfram-like syndrome; WS: Wolfram syndrome; WT: wild-type.

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