Role of Muscle LIM Protein in Mechanotransduction Process

Abstract

The induction of protein synthesis is crucial to counteract the deconditioning of neuromuscular system and its atrophy. In the past, hormones and cytokines acting as growth factors involved in the intracellular events of these processes have been identified, while the implications of signaling pathways associated with the anabolism/catabolism ratio in reference to the molecular mechanism of skeletal muscle hypertrophy have been recently identified. Among them, the mechanotransduction resulting from a mechanical stress applied to the cell appears increasingly interesting as a potential pathway for therapeutic intervention. At present, there is an open question regarding the type of stress to apply in order to induce anabolic events or the type of mechanical strain with respect to the possible mechanosensing and mechanotransduction processes involved in muscle cells protein synthesis. This review is focused on the muscle LIM protein (MLP), a structural and mechanosensing protein with a LIM domain, which is expressed in the sarcomere and costamere of striated muscle cells. It acts as a transcriptional cofactor during cell proliferation after its nuclear translocation during the anabolic process of differentiation and rebuilding. Moreover, we discuss the possible opportunity of stimulating this mechanotransduction process to counteract the muscle atrophy induced by anabolic versus catabolic disorders coming from the environment, aging or myopathies.

Keywords: MLP; atrophy; mechanotransduction; prophylaxis; striated muscle; ultrasound stimulation.

Figure 1

Relationship between the costamere and the sarcolemma, the extracellular matrix and the sarcolemma and, the sarcolemma and the nucleus. The drawings of costamere zone, extracellular zone and the nucleus zone are inspired from Samarel et al. [100], Nishimura [77], Wang et al. [75] and Henderson et al. [101], respectively. Red arrows: longitudinal force transmission. Yellow arrows: Lateral force transmission. An example is shown on the possible mechanical stress induced by an external pressure or internal sarcomeric contraction.

Figure 2

Proposition of events implying the mechanotransduction process induced by MLP following mechanical stimulation. Shown are the different molecular partners that are involved during the cross-talk between the extracellular matrix (ECM) and intracellular matrix (ICM) upon mechanical stimuli. The dual role of MLP as a structural protein in its polymeric form and as a functional protein in its activated monomeric form that plays the role of cofactor of MyoD, MRF4, and myogenin transcription factors. Post-translational modifications as phosphorylation or sumoylation of monomeric MLP triggers its shuttling to the nucleus. Inspired and modified from [9].