Biochemical and proteomic insights into sarcoplasmic reticulum Ca²⁺-ATPase complexes in skeletal muscles

ABSTRACT

Introduction

Skeletal muscles contain large numbers of high-molecular-mass protein complexes in elaborate membrane systems. Integral membrane proteins are involved in diverse cellular functions including the regulation of ion handling, membrane homeostasis, energy metabolism and force transmission.

Areas covered

The proteomic profiling of membrane proteins and large protein assemblies in skeletal muscles are outlined in this article. This includes a critical overview of the main biochemical separation techniques and the mass spectrometric approaches taken to study membrane proteins. As an illustrative example of an analytically challenging large protein complex, the proteomic detection and characterization of the Ca²⁺-ATPase of the sarcoplasmic reticulum is discussed. The biological role of this large protein complex during normal muscle functioning, in the context of fiber type diversity and in relation to mechanisms of physiological adaptations and pathophysiological abnormalities is evaluated from a proteomics perspective.

Expert opinion

Mass spectrometry-based muscle proteomics has decisively advanced the field of basic and applied myology. Although it is technically challenging to study membrane proteins, innovations in protein separation methodology in combination with sensitive mass spectrometry and improved systems bioinformatics has allowed the detailed proteomic detection and characterization of skeletal muscle membrane protein complexes, such as Ca²⁺-pump proteins of the sarcoplasmic reticulum.

KEYWORDS:

• Calcium ATPase
• calcium homeostasis
• calcium pump
• membrane protein
• muscle relaxation
• sarcoplasmic reticulum
• SERCA

Article highlights

• Comparative proteomics has been helpful to establish abundance changes of SERCA-type Ca²⁺-ATPases in various diseases, such as cancer cachexia, myotonia, motor neuron disease and muscular dystrophy

• Sarcoplasmic reticulum Ca²⁺-ATPases are responsible for the swift re-uptake of Ca²⁺-ions during skeletal muscle relaxation

• The SERCA1 and SERCA2 isoforms of the sarcoplasmic reticulum Ca²⁺-ATPases are expressed in a fiber type specific way in skeletal muscle

• Mass spectrometry-based proteomics has been instrumental in the detection and characterization of SERCA isoforms

• Single cell proteomics has been used to study SERCA expression patterns in fast versus slow muscle fiber populations

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the Kathleen Lonsdale Institute for Human Health Research at Maynooth University, and Science Foundation Ireland Infrastructure Award [SFI‑12/RI/2346/3].