Tension and Force-Resistant Attachment Are Essential for Myofibrillogenesis in Drosophila Flight Muscle

Weitkunat, Manuela; Kaya-Çopur, Aynur; Grill, Stephan W.; Schnorrer, Frank

doi:10.1016/j.cub.2014.02.032

Cited by 122 publications

(185 citation statements)

References 54 publications

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“…One possibility is that Kon helps to localize integrins at the MTJ. In fact, it has been shown that Kon helps to localize integrins at the MTJ in adult flight muscles (Weitkunat et al, 2014), although this is not the case in adult abdominal muscles (Perez-Moreno et al, 2014). Here, we have found that Kon does not regulate αPS2βPS integrin localization at the MTJ in Drosophila embryos.…”

Section: Discussionsupporting

confidence: 46%

“…Kon is essential for the targeting and adhesion between embryonic muscles and tendons (Estrada et al, 2007;Schnorrer et al, 2007), both in the embryo and in the adult (Perez-Moreno et al, 2014;Weitkunat et al, 2014). The molecular nature of Kon and its vertebrate ortholog CSPG4, together with some experimental data, indicates that they function as ECM receptors (Couchman, 2010;Staub et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction

Pérez-Moreno

Espina-Zambrano

García-Calderón

et al. 2017

Journal of Cell Science

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Cell-extracellular-matrix adhesion is mediated by cell receptors, mainly integrins and transmembrane proteoglycans, which can functionally interact. How these receptors are regulated and coordinated is largely unknown. We show that the conserved transmembrane Drosophila proteoglycan Kon-tiki (Kon, also known as Perdido) interacts with the αPS2βPS integrin (αPS2 is encoded by inflated and βPS by myospheroid) to mediate muscle-tendon adhesion. kon and inflated double mutant embryos show a synergistic increase in muscle detachment. Furthermore, Kon modulates αPS2βPS signaling at the muscle attachment, since phosphorylated Fak is reduced in kon mutants. This reduction in integrin signaling can be rescued by the expression of a truncated Kon protein containing its transmembrane and extracellular domains, suggesting that these domains are sufficient to mediate this signaling. We show that these domains are sufficient to properly localize the αPS2βPS ligand, Thrombospondin, to the muscle attachment, and to partially rescue Kon-dependent muscle-tendon adhesion. We propose that Kon can engage in a protein complex with αPS2βPS and enhance integrin-mediated signaling and adhesion by recruiting its ligand, which would increase integrin-binding affinity to the extracellular matrix, resulting in the consolidation of the myotendinous junction.

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Section: Discussionsupporting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction

Pérez-Moreno

Espina-Zambrano

García-Calderón

et al. 2017

Journal of Cell Science

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“…Through these interactions, obscurin can potentially be linked to a receptor tyrosine kinase (RTK) pathway involved in myogenesis. Obscurin and Kettin are present at an early stage in the development of pupal IFM (Katzemich et al, 2012;Weitkunat et al, 2014). Both are large titin-like proteins with tandem Ig domains, which have a dual function in myogenesis and in the mature muscle.…”

Section: Discussionmentioning

confidence: 99%

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

Katzemich

West

Fukuzawa

et al. 2015

Journal of Cell Science

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Drosophila obscurin (Unc-89) is a titin-like protein in the M-line of the muscle sarcomere. Obscurin has two kinase domains near the C-terminus, both of which are predicted to be inactive. We have identified proteins binding to the kinase domains. Kinase domain 1 bound Bällchen (Ball, an active kinase), and both kinase domains 1 and 2 bound MASK (a 400-kDa protein with ankyrin repeats). Ball was present in the Z-disc and M-line of the indirect flight muscle (IFM) and was diffusely distributed in the sarcomere. MASK was present in both the M-line and the Z-disc. Reducing expression of Ball or MASK by siRNA resulted in abnormalities in the IFM, including missing M-lines and multiple Z-discs. Obscurin was still present, suggesting that the kinase domains act as a scaffold binding Ball and MASK. Unlike obscurin in vertebrate skeletal muscle, Drosophila obscurin is necessary for the correct assembly of the IFM sarcomere. We show that Ball and MASK act downstream of obscurin, and both are needed for development of a well defined M-line and Z-disc. The proteins have not previously been identified in Drosophila muscle.

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“…These premyofibrils subsequently exchange their nonmuscle myosin II for muscle myosin II and extend throughout the fiber (Sparrow and Schock 2009). A recent study in Drosophila has highlighted the importance of mechanical tension, generated through the attachment of the growing muscle fibers to tendons, in the assembly of sarcomeres (Weitkunat et al 2014). We see no evidence of defects in the vertical myosepta to which skeletal muscle fibers attach, nor of a failure of attachment of the fast-twitch fibers, arguing against this being a primary cause of myofibrillogenesis failure in fro mutants.…”

Section: Discussionmentioning

confidence: 99%

A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B

et al. 2017

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Myosin 18B is an unconventional myosin that has been implicated in tumor progression in humans. In addition, loss-offunction mutations of the MYO18B gene have recently been identified in several patients exhibiting symptoms of nemaline myopathy. In mouse, mutation of Myo18B results in early developmental arrest associated with cardiomyopathy, precluding analysis of its effects on skeletal muscle development. The zebrafish, frozen (fro) mutant was identified as one of a group of immotile mutants in the 1996 Tübingen genetic screen. Mutant embryos display a loss of birefringency in their skeletal muscle, indicative of disrupted sarcomeric organization. Using meiotic mapping, we localized the fro locus to the previously unannotated zebrafish myo18b gene, the product of which shares close to 50% identity with its human ortholog. Transcription of myo18b is restricted to fast-twitch myocytes in the zebrafish embryo; consistent with this, fro mutant embryos exhibit defects specifically in their fast-twitch skeletal muscles. We show that sarcomeric assembly is blocked at an early stage in fro mutants, leading to the disorganized accumulation of actin, myosin, and a-actinin and a complete loss of myofibrillar organization in fast-twitch muscles.

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Tension and Force-Resistant Attachment Are Essential for Myofibrillogenesis in Drosophila Flight Muscle

Cited by 122 publications

References 54 publications

Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction

Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction

Binding partners of the kinase domains inDrosophilaobscurin and their effect on the structure of the flight muscle

A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B

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