Composite biopolymer scaffolds shape muscle nucleus: Insights and perspectives fromDrosophila

Abstract

Contractile muscle fibers produce enormous intrinsic forces during contraction/relaxation waves. These forces are directly applied to their cytoplasmic organelles including mitochondria, sarcoplasmic reticulum, and multiple nuclei. Data from our analysis of Drosophila larval somatic muscle fibers suggest that an intricate network of organized microtubules (MT) intermingled with Spectrin-Repeat-Containing Proteins (SRCPs) are major structural elements that protect muscle organelles and maintain their structure and position during muscle contraction. Whereas the perinuclear MT network provides structural rigidity to the myonucleus, the SRCPs Nesprin and Spectraplakin form semiflexible filamentous biopolymer networks, providing nuclei with the elasticity required to resist the contractile cytoplasmic forces produced by the muscle. Spectrin repeats are domains found in numerous structural proteins, which are able to unfold under tension and are subject to mechanical stresses in the cell. This unique composite scaffold combines rigidity and resilience in order to neutralize the oscillating cellular forces occurring during muscle contraction/ relaxation waves and thereby protect myonuclei. We suggest that the elastic properties of SRCPs are critical for nuclear protection and proper function in muscle fibers.

Microtubule Organization in Striated Muscle Cells

“…Muscle contraction generates substantial force which exerts strain on cellular organelles [233]. Preserving intracellular architecture against stress from numerous contraction/relaxation cycles is pivotal for proper muscle cell function [233].…”

“…Muscle contraction generates substantial force which exerts strain on cellular organelles [233]. Preserving intracellular architecture against stress from numerous contraction/relaxation cycles is pivotal for proper muscle cell function [233]. The nucleus, considered to be the largest and stiffest organelle in many mammalian cells [234], especially needs to be protected in order to maintain genomic integrity [235,236].…”

Genetic Control of Muscle Diversification and Homeostasis: Insights from Drosophila

“…Integrin and IAP stoichiometries at the MTJ are important to respond to different types of forces [ 166 ]. The myonuclear LINC complex and associated components such as Msp300 and Spectraplakin, which regulate MT organization, play a role in myonuclear maintenance by providing elasticity to resist contractile forces with the help of the MT network that surrounds it [ 281 , 282 , 283 ]. In addition, Msp300 associates with the Z-disc and keeps the mitochondria and SR anchored to the Z-disc during contractions [ 284 ].…”

Nuclear morphologies: their diversity and functional relevance

“…They act as linkers within the nuclear envelope proteins, and to the cytoskeleton or the nucleoskeleton (Rajgor and Shanahan 2013). The role of spectrins outside the nucleus has been well studied; they help to provide the flexibility and elasticity that smooth muscle nuclei and other organelles require during contraction (Wang and Volk 2015; King and Lusk 2016). They also appear to have a role in the development of nuclear shape in sperm; in falciform sperm, such as from rats, spectrin has been found to be associated with the apical hook (Dvořáková et al 2005), suggesting a contribution to the development of the sperm shape, as well as a functional contribution to capacitation and the acrosome reaction (Bastián et al 2010).…”