Characterization of the dystrophin-associated protein complex by mass spectrometry

Authors

Emily H. Canessa, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.
Rita Spathis, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.
James S. Novak, Center for Genetic Medicine Research, Children's National Research Institute, Children's National Hospital, Washington, District of Columbia, USA.
Aaron Beedle, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.
Kanneboyina Nagaraju, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.
Luca Bello, Department of Neuroscience, ERN Neuromuscular Center, University of Padova, Padua, Italy.
Elena Pegoraro, Department of Neuroscience, ERN Neuromuscular Center, University of Padova, Padua, Italy.
Eric P. Hoffman, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.
Yetrib Hathout, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, SUNY, Binghamton, New York, USA.

Document Type

Journal Article

Publication Date

11-24-2022

Journal

Mass spectrometry reviews

DOI

10.1002/mas.21823

Keywords

dystroglycans; dystrophin; laminin; mass spectrometry; sarcoglycans

Abstract

The dystrophin-associated protein complex (DAPC) is a highly organized multiprotein complex that plays a pivotal role in muscle fiber structure integrity and cell signaling. The complex is composed of three distinct interacting subgroups, intracellular peripheral proteins, transmembrane glycoproteins, and extracellular glycoproteins subcomplexes. Dystrophin protein nucleates the DAPC and is important for connecting the intracellular actin cytoskeletal filaments to the sarcolemma glycoprotein complex that is connected to the extracellular matrix via laminin, thus stabilizing the sarcolemma during muscle fiber contraction and relaxation. Genetic mutations that lead to lack of expression or altered expression of any of the DAPC proteins are associated with different types of muscle diseases. Hence characterization of this complex in healthy and dystrophic muscle might bring insights into its role in muscle pathogenesis. This review highlights the role of mass spectrometry in characterizing the DAPC interactome as well as post-translational glycan modifications of some of its components such as α-dystroglycan. Detection and quantification of dystrophin using targeted mass spectrometry are also discussed in the context of healthy versus dystrophic skeletal muscle.

APA Citation

Canessa, Emily H.; Spathis, Rita; Novak, James S.; Beedle, Aaron; Nagaraju, Kanneboyina; Bello, Luca; Pegoraro, Elena; Hoffman, Eric P.; and Hathout, Yetrib, "Characterization of the dystrophin-associated protein complex by mass spectrometry" (2022). GW Authored Works. Paper 1902.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1902

Department

Genomics and Precision Medicine