In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-23), p. e1010287-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010287
DOI:
10.1371/journal.pgen.1010287.g001
DOI:
10.1371/journal.pgen.1010287.g002
DOI:
10.1371/journal.pgen.1010287.g003
DOI:
10.1371/journal.pgen.1010287.g004
DOI:
10.1371/journal.pgen.1010287.g005
DOI:
10.1371/journal.pgen.1010287.g006
DOI:
10.1371/journal.pgen.1010287.g007
DOI:
10.1371/journal.pgen.1010287.s001
DOI:
10.1371/journal.pgen.1010287.s002
DOI:
10.1371/journal.pgen.1010287.s003
DOI:
10.1371/journal.pgen.1010287.s004
DOI:
10.1371/journal.pgen.1010287.s005
DOI:
10.1371/journal.pgen.1010287.s006
DOI:
10.1371/journal.pgen.1010287.s007
DOI:
10.1371/journal.pgen.1010287.s008
DOI:
10.1371/journal.pgen.1010287.s009
DOI:
10.1371/journal.pgen.1010287.s010
DOI:
10.1371/journal.pgen.1010287.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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