Characterization of δ-Sarcoglycan, a Novel Component of the Oligomeric Sarcoglycan Complex Involved in Limb-Girdle Muscular Dystrophy

doi:10.1074/jbc.271.50.32321

Characterization of δ-Sarcoglycan, a Novel Component of the Oligomeric Sarcoglycan Complex Involved in Limb-Girdle Muscular Dystrophy*

From the ^¶ Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, the
^″ Department of Biological Chemistry, University of California, Irvine, Irvine, California 92717, the
^‴ Howard Hughes Medical Institute, Biopolymer Facility, University of Texas Southwestern Medical Center, Dallas, Texas 75235, the
^† Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21287-8811, and the
^§§ Department of Genetics/Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri 63108

^¶¶ Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed:
Howard Hughes Medical Institute, Dept. of Physiology and Biophysics, University of Iowa College of Medicine, 400 Eckstein Medical Research Bldg., Iowa City, IA 52242-1101.
Tel.: 319-335-7867; Fax: 319-335-6957; E-mail: kevin-campbell{at}uiowa.edu; WWW: http://www-camlab.physlog.uiowa.edu/home.htm.

↵^∥ These authors contributed equally to this work.

Abstract

The sarcoglycan complex is known to be involved in limb-girdle muscular dystrophy (LGMD) and is composed of at least three proteins: α-, β-, and γ-sarcoglycan. δ-Sarcoglycan has now been identified as a second 35-kDa sarcolemmal transmembrane glycoprotein that shares high homology with γ-sarcoglycan and is expressed mainly in skeletal and cardiac muscle. Biochemical analysis has demonstrated that γ- and δ-sarcoglycan are separate entities within the sarcoglycan complex and that all four sarcoglycans exist in the complex on a stoichiometrically equal basis. Immunohistochemical analysis of skeletal muscle biopsies from patients with LGMD2C, LGMD2D, and LGMD2E demonstrated a reduction of the entire sarcoglycan complex in these muscular dystrophies. Furthermore, we have mapped the human δ-sarcoglycan gene to chromosome 5q33-q34 in a region overlapping the recently linked autosomal recessive LGMD2F locus.

Footnotes

↵* This work was supported in part by the Muscular Dystrophy Association. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

DGC

dystrophin-glycoprotein complex

DMD

Duchenne muscular dystrophy

LGMD

limb-girdle muscular dystrophy

BSA

bovine serum albumin

PCR

polymerase chain reaction

PBS

phosphate-buffered saline

FITC

fluoroisothiocyanate

PAGE

polyacrylamide gel electrophoresis

HPLC

high pressure liquid chromatography.
↵² D. Jung, unpublished results.
- Received August 8, 1996.