TAGC 2020 poster .pdf (1.14 MB)
A Role for UNC-45 in Maintaining Myosin During Aging
poster
posted on 2020-04-20, 23:03 authored by Courtney Christian, Hiroshi Qadota, Guy M. BenianUsing immunostaining with antibodies to myosin
heavy chain A (MHC A), we show that there is a gradual decline in motility
beginning at day 4 and the number of A-bands (a measure of thick filament
assembly) beginning at day 8 adults. By day 12 and especially day 16, there is
also disorganization of A-bands. This disorganization appears similar
to that
of unc-45 ts
mutants grown at the restrictive temperature. We have found that in C.
elegans a
decline in hsp-90 mRNA
(day 2) directly precedes a decline in HSP-90 protein (day3), which directly
precedes a decline in UNC-45 protein (day4), which then in turn precedes a
decline in Myosin B (day8), the main client of UNC-45. unc-45,
unc-54, and myo-3 mRNA
decline immediately after reaching maturity (day 1) and remain stable, though
low – which is expected for proteins assembled into the sarcomere. We also
observe a decrease in UNC-45 protein, but not mRNA, in an hsp-90 loss
of function mutant, suggesting a role for HSP-90 in UNC-45 regulation and/or
protein stabilization. We also observe early onset of sarcopenia when UNC-45 is
lost during adulthood and an increase in an unknown UNC-45 post translational
modification with age.
Funding
The UNC-45 Chaperone as a Modulator of Myosin Biogenesis and Function
National Institute of General Medical Sciences
Find out more...