Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance.

Abstract

X-linked Emery-Dreifuss muscular dystrophy is caused by loss of function of emerin, an integral protein of the inner nuclear membrane. Yet emerin null mice are essentially normal, suggesting the existence of a critical compensating factor. We show that the lamina-associated polypeptide1 (LAP1) interacts with emerin. Conditional deletion of LAP1 from striated muscle causes muscular dystrophy; this pathology is worsened in the absence of emerin. LAP1 levels are significantly higher in mouse than human skeletal muscle, and reducing LAP1 by approximately half in mice also induces muscle abnormalities in emerin null mice. Conditional deletion of LAP1 from hepatocytes yields mice that exhibit normal liver function and are indistinguishable from littermate controls. These results establish that LAP1 interacts physically and functionally with emerin and plays an essential and selective role in skeletal muscle maintenance. They also highlight how dissecting differences between mouse and human phenotypes can provide fundamental insights into disease mechanisms.

• Authors: Ji-Yeon Shin, Iván Méndez-López, Yuexia Wang, Arthur P Hays, Kurenai Tanji, Jay H Lefkowitch, P Christian Schulze, Howard J Worman, William T Dauer
• Journal: Developmental cell (Dev Cell) Vol. 26 Issue 6 Pg. 591-603 (Sep 30 2013) ISSN: 1878-1551 [Electronic] United States
• PMID: 24055652 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• Membrane Proteins
• Nuclear Proteins
• TNF Receptor-Associated Factor 3
• TOR1AIP1 protein, human
• emerin

Topics

• Animals
• Cells, Cultured
• Cytoskeletal Proteins
• Fibroblasts (metabolism)
• Gene Deletion
• HEK293 Cells
• Hepatocytes (metabolism)
• Humans
• Liver (metabolism, physiology)
• Membrane Proteins (genetics, metabolism)
• Mice
• Muscle, Skeletal (metabolism, pathology)
• Muscular Dystrophy, Emery-Dreifuss (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Protein Binding
• TNF Receptor-Associated Factor 3 (genetics, metabolism)