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Fig. 3 | BMC Medicine

Fig. 3

From: Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy

Fig. 3

Hippo signaling pathway components modify the Dg-linked muscle degeneration phenotype. a Scheme of the Hippo kinase signal transduction pathway, major components of which are evolutionarily conserved from flies to humans. Kbr is a Hippo signaling activator. Wts/Lats phosphorylates transcriptional co-activator Yki, which prevents its relocation from the cytosol to the nucleus. Two components of the pathway Kbr (orange) and Yki (yellow) were identified by the mass spectrometry analysis to be associated with the Dg protein. b Bar graph represents the quantification of the moderate and strong IFM degeneration phenotypes (blue and red bars, respectively) in young (7-day-old) and aged (28-day-old) animals (Additional file 2: Table S5). Aging per se causes significant muscle degeneration (see 28-day-old control w1118/+, and black stars indicate statistical significance. Reduction of Dg, kbr, or yki by one copy additionally increases moderate—and in particular, strong—muscle degeneration in old animals (see 28-day-old DgO55/+, ykiB5/+, kbrdel/+ and blue stars for statistics). The introduction of the Hippo pathway mutations into a Dg heterozygous background significantly modifies the age-dependent muscle degeneration phenotype (Additional file 2: Table S5). In particular, the reduction of yki by one copy suppresses (see DgO55/ykiB5 and green stars for statistics), while reduction of Kbr by one copy enhances (see DgO55/+, kbrdel/+, and pink stars for statistics) the frequency of muscle degeneration observed in Dg heterozygous mutants. cf Hematoxylin and eosin (H&E)-stained transverse sections of indirect flight muscles (IFMs) of 28-day-old control (w1118/+), Dg heterozygous (DgO55/+), Dg and yki trans-heterozygous (DgO55/ykiB5), and Dg and kbr trans-heterozygous (DgO55/+, kbrdel/+) animals. Blue and red arrows point to moderate and strong muscle degeneration, respectively

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