Journal Article

Unusual 5′ Transcript Complexity of Plectin Isoforms: Novel Tissue-Specific Exons Modulate Actin Binding Activity

Peter Fuchs, Michael Zörer, Günther A. Rezniczek, Daniel Spazierer, Susanne Oehler, Maria J. Castañón, Rudolf Hauptmann and Gerhard Wiche

in Human Molecular Genetics

Volume 8, issue 13, pages 2461-2472
Published in print December 1999 | ISSN: 0964-6906
Published online December 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.13.2461
Unusual 5′ Transcript Complexity of Plectin Isoforms: Novel Tissue-Specific Exons Modulate Actin Binding Activity

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Plectin, the most versatile cytolinker identified to date, has essential functions in maintaining the mechanical integrity of skin, skeletal muscle and heart, as indicated by analyses of plectin-deficient mice and humans. Expression of plectin in a vast variety of tissues and cell types, combined with a large number of different binding partners identified at the molecular level, calls for complex mechanisms regulating gene transcription and expression of the protein. To investigate these mechanisms, we analyzed the transcript diversity and genomic organization of the murine plectin gene and found a remarkable complexity of its 5′-end structure. An unusually high number of 14 alternatively spliced exons, 11 of them directly splicing into plectin exon 2, were identified. Analysis of their tissue distribution revealed that expression of a few of them is restricted to tissues such as brain, or skeletal muscle and heart. In addition, we found two short exons tissue-specifically spliced into a highly conserved set of exons encoding the N-terminal actin binding domain (ABD), common to plectin and the superfamily of spectrin/dystrophin-type actin binding proteins. Using recombinant proteins we show that a novel ABD version contained in the muscle-specific isoform of plectin exhibits significantly higher actin binding activity than other splice forms. This fine tuning mechanism based on alternative splicing is likely to optimize the proposed biological role of plectin as a cytolinker opposing intense mechanical forces in tissues like striated muscle.

Journal Article.  7741 words.  Illustrated.

Subjects: Genetics and Genomics

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