English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy.

Yatsenko, A. S., Kucherenko, M. M., Xie, Y., Aweida, D., Urlaub, H., Scheibe, R. J., et al. (2020). Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy. BMC Medicine, 18(1): 8. doi:10.1186/s12916-019-1478-3.

Item is

Files

show Files
hide Files
:
3188384.pdf (Publisher version), 15MB
Name:
3188384.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
:
3188384_Suppl_1.xlsx (Supplementary material), 436KB
Name:
3188384_Suppl_1.xlsx
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
3188384_Suppl_2.pdf (Supplementary material), 5MB
Name:
3188384_Suppl_2.pdf
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Yatsenko, A. S., Author
Kucherenko, M. M.1, Author           
Xie, Y., Author
Aweida, D., Author
Urlaub, H.2, Author           
Scheibe, R. J., Author
Cohen, S., Author
Shcherbata, H. R.1, Author           
Affiliations:
1Research Group of Gene Expression and Signaling, MPI for biophysical chemistry, Max Planck Society, ou_578608              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

Content

show
hide
Free keywords: Dystroglycan; Hippo kinase signaling; Kibra; Muscle atrophy; Muscle degeneration; Muscular dystrophies; Proteomics; Yorkie
 Abstract: Dystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular, Drosophila is amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex.
METHODS:

To identify new players contributing to dystroglycanopathies, we used Drosophila as a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates.
RESULTS:

The muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity.
CONCLUSIONS:

The results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression.

Details

show
hide
Language(s): eng - English
 Dates: 2020-01-21
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1186/s12916-019-1478-3
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: BMC Medicine
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 26 Volume / Issue: 18 (1) Sequence Number: 8 Start / End Page: - Identifier: -