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PMID: 8120103 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin.

The Journal of cell biology ·Vol. 124 ·No. 5 ·1994-03-00 ·Pages 827-41

Li H, Choudhary SK, Milner DJ, Munir MI, Kuisk IR, Capetanaki Y

Abstract

The muscle-specific intermediate filament protein, desmin, is one of the earliest myogenic markers whose functional role during myogenic commitment and differentiation is unknown. Sequence comparison of the presently isolated and fully characterized mouse desmin cDNA clones revealed a single domain of polypeptide similarity between desmin and the basic and helix-loop-helix region of members of the myoD family myogenic regulators. This further substantiated the need to search for the function of desmin. Constructs designed to express anti-sense desmin RNA were used to obtain stably transfected C2C12 myoblast cell lines. Several lines were obtained where expression of the anti-sense desmin RNA inhibited the expression of desmin RNA and protein down to basal levels. As a consequence, the differentiation of these myoblasts was blocked; complete inhibition of myoblast fusion and myotube formation was observed. Rescue of the normal phenotype was achieved either by spontaneous revertants, or by overexpression of the desmin sense RNA in the defective cell lines. In several of the cell lines obtained, inhibition of desmin expression was followed by differential inhibition of the myogenic regulators myoD and/or myogenin, depending on the stage and extent of desmin inhibition in these cells. These data suggested that myogenesis is modulated by at least more than one pathway and desmin, which so far was believed to be merely an architectural protein, seems to play a key role in this process.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Fusion Cell Line Consensus Sequence DNA, Complementary/metabolism Desmin/antagonists & inhibitors,biosynthesis Gene Expression/drug effects Helix-Loop-Helix Motifs Mice Molecular Sequence Data Muscles/cytology,metabolism,physiology MyoD Protein/antagonists & inhibitors,biosynthesis,metabolism Myogenin/antagonists & inhibitors,biosynthesis,metabolism RNA, Antisense/pharmacology RNA, Messenger/biosynthesis Sequence Homology, Amino Acid Transfection
Chemicals
DNA, Complementary Desmin MyoD Protein Myog protein, mouse Myogenin RNA, Antisense RNA, Messenger
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li H
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Choudhary S K
Milner D J
Munir M I
Kuisk I R
Capetanaki Y
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.124.5.827
Published
1994-03-00
Pages
827-41
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119944
Subset
IM
Grants
NIAMS NIH HHS · AR39617-01 · United States
Databases
GENBANK
L22550
External Links
PubMed source DOI: 10.1083/jcb.124.5.827 PMC Full Text View journal details
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