Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms

Patryk Konieczny, Peter Fuchs, Siegfried Reipert, Wolfram S. Kunz, A. Zeöld, Irmgard Fischer, Denise Paulin, Rolf Schröder, Gerhard Wiche

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Dysfunction of plectin, a 500-kD cytolinker protein, leads to skin blistering and muscular dystrophy. Using conditional gene targeting in mice, we show that plectin deficiency results in progressive degenerative alterations in striated muscle, including aggregation and partial loss of intermediate filament (IF) networks, detachment of the contractile apparatus from the sarcolemma, profound changes in myofiber costameric cytoarchitecture, and decreased mitochondrial number and function. Analysis of newly generated plectin isoform-specific knockout mouse models revealed that IF aggregates accumulate in distinct cytoplasmic compartments, depending on which isoform is missing. Our data show that two major plectin isoforms expressed in muscle, plectin 1d and 1f, integrate fibers by specifically targeting and linking desmin IFs to Z-disks and costameres, whereas plectin 1b establishes a linkage to mitochondria. Furthermore, disruption of Z-disk and costamere linkages leads to the pathological condition of epidermolysis bullosa with muscular dystrophy. Our fi ndings establish plectin as the major organizer of desmin IFs in myofibers and provide new insights into plectin- and desmin-related muscular dystrophies.

Original languageEnglish
Pages (from-to)667-681
Number of pages15
JournalJournal of Cell Biology
Volume181
Issue number4
DOIs
Publication statusPublished - May 19 2008

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Costameres
Plectin
Desmin
Protein Isoforms
Muscular Dystrophies
Intermediate Filaments
Plakins
Epidermolysis Bullosa
Sarcolemma
Striated Muscle
Gene Targeting
Knockout Mice
Mitochondria

ASJC Scopus subject areas

  • Cell Biology

Cite this

Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. / Konieczny, Patryk; Fuchs, Peter; Reipert, Siegfried; Kunz, Wolfram S.; Zeöld, A.; Fischer, Irmgard; Paulin, Denise; Schröder, Rolf; Wiche, Gerhard.

In: Journal of Cell Biology, Vol. 181, No. 4, 19.05.2008, p. 667-681.

Research output: Contribution to journalArticle

Konieczny, P, Fuchs, P, Reipert, S, Kunz, WS, Zeöld, A, Fischer, I, Paulin, D, Schröder, R & Wiche, G 2008, 'Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms', Journal of Cell Biology, vol. 181, no. 4, pp. 667-681. https://doi.org/10.1083/jcb.200711058
Konieczny, Patryk ; Fuchs, Peter ; Reipert, Siegfried ; Kunz, Wolfram S. ; Zeöld, A. ; Fischer, Irmgard ; Paulin, Denise ; Schröder, Rolf ; Wiche, Gerhard. / Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. In: Journal of Cell Biology. 2008 ; Vol. 181, No. 4. pp. 667-681.
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