The conserved transmembrane proteoglycan Perdido/Kon-tiki is essential for myofibrillogenesis and sarcomeric structure in Drosophila

Abstract

Muscle differentiation requires the assembly of high-order structures called myofibrils, composed of sarcomeres. Even though the molecular organization of sarcomeres is well known, the mechanisms underlying myofibrillogenesis are poorly understood. It has been proposed that integrin-dependent adhesion nucleates myofibrils at the periphery of the muscle cell to sustain sarcomere assembly. Here, we report a role for the gene perdido (perd, also known as kon-tiki, a transmembrane chondroitin proteoglycan) in myofibrillogenesis. Expression of perd RNAi in muscles, prior to adult myogenesis, can induce misorientation and detachment of Drosophila adult abdominal muscles. In comparison to controls, perd-depleted muscles contain fewer myofibrils, which are localized at the cell periphery. These myofibrils are detached from each other and display a defective sarcomeric structure. Our results demonstrate that the extracellular matrix receptor Perd has a specific role in the assembly of myofibrils and in sarcomeric organization. We suggest that Perd acts downstream or in parallel to integrins to enable the connection of nascent myofibrils to the Z-bands. Our work identifies the Drosophila adult abdominal muscles as a model to investigate in vivo the mechanisms behind myofibrillogenesis.

A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle

“…Is this a general concept for sarcomere morphogenesis? Reviewing the literature, one finds that in other Drosophila muscle types which display a tubular cross-striated myofibril organisation, such as the fly abdominal muscles, the striated sarcomeres also first assemble and then grow in length ( PerezPérez-Moreno et al, 2014 ; Weitkunat et al, 2017 ), suggesting a conserved mechanism. In developing zebrafish skeletal muscles, young myofibers present in younger somites show a short sarcomere length of about 1.2 µm, which increases to about 2.3 µm when somites and muscle fibers mature ( Sanger et al, 2017 ; Sanger et al, 2009 ).…”

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

“…Perdido/Kon-tiki , the Drosophila ortholog of mammalian CSPG4 , genetically interacts with integrins during Drosophila embryogenesis, and its loss is embryonic lethal [ 62 ]. RNAi-mediated suppression of Perdido/Kon-tiki in the muscles, just before adult myogenesis starts, induces misorientation and detachment of Drosophila adult abdominal muscle, generating a phenotype similar to the embryonic lethal ones [ 63 ]. Thus, it is possible that, based on its high conservation through species, mammalian CSPG4 could also play a role in myogenesis and function as well.…”

Ectopic Expression Screen Identifies Genes AffectingDrosophilaMesoderm Development Including the HSPG Trol

“…Adhesion may also be impacted by CSPGs ( Perez-Moreno et al 2014 ). Our screen identified PTP99A, which is predicted to be a CSPG; the only other in Drosophila is Kon ( Song et al 2012 ).…”

“…These CSPGs may regulate adhesion, like integrins, and/or FGF ligand-receptor interactions, like HSPGs. Kon is an ortholog of mammalian CSPG4 ( Perez-Moreno et al 2014 ) and shows defects in CVM migration ( Figure 7K ). Ptp99a shares sequence homology with the CSPG Phosphocan only across their cytoplasmic phosphatase regions.…”