Mob4-dependent STRIPAK involves the chaperonin TRiC to coordinate myofibril and microtubule network growth
Myofibrils of the skeletal muscle are comprised of sarcomeres that generate force by contraction when myosin-rich thick filaments slide past actin-based thin filaments. Surprisingly little is known about the molecular processes that guide sarcomere assembly in vivo , despite deficits within this pro...
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Published in | PLoS genetics Vol. 18; no. 6; p. e1010287 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
San Francisco
Public Library of Science
01.06.2022
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Myofibrils of the skeletal muscle are comprised of sarcomeres that generate force by contraction when myosin-rich thick filaments slide past actin-based thin filaments. Surprisingly little is known about the molecular processes that guide sarcomere assembly
in vivo
, despite deficits within this process being a major cause of human disease. To overcome this knowledge gap, we undertook a forward genetic screen coupled with reverse genetics to identify genes required for vertebrate sarcomere assembly. In this screen, we identified a zebrafish mutant with a nonsense mutation in
mob4
. In
Drosophila
,
mob4
has been reported to play a role in spindle focusing as well as neurite branching and in planarians
mob4
was implemented in body size regulation. In contrast, zebrafish
mob4
geh
mutants are characterised by an impaired actin biogenesis resulting in sarcomere defects. Whereas loss of
mob4
leads to a reduction in the amount of myofibril, transgenic expression of
mob4
triggers an increase. Further genetic analysis revealed the interaction of Mob4 with the actin-folding chaperonin TRiC, suggesting that Mob4 impacts on TRiC to control actin biogenesis and thus myofibril growth. Additionally,
mob4
geh
features a defective microtubule network, which is in-line with tubulin being the second main folding substrate of TRiC. We also detected similar characteristics for
strn3
-deficient mutants, which confirmed Mob4 as a core component of STRIPAK and surprisingly implicates a role of the STRIPAK complex in sarcomerogenesis. |
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Bibliography: | new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. |
ISSN: | 1553-7404 1553-7390 1553-7404 |
DOI: | 10.1371/journal.pgen.1010287 |