UNC-89 (obscurin) binds to MEL-26, a BTB-domain protein, and affects the function of MEI-1 (katanin) in striated muscle ofCaenorhabditis elegans

Abstract

UNC-89 (obscurin) interacts with MEL-26, a BTB-domain protein/adaptor for cullin-3. MEL-26 colocalizes with UNC-89 at M-lines. Mutations in MEL-26, CUL-3 (cullin-3), and MEI-1 (katanin) result in a muscle phenotype similar to that of unc-89 mutants. The level of MEI-1 is reduced in unc-89 mutants, suggesting that normally UNC-89 inhibits CUL-3/MEL-26 in muscle.

Development, structure, and maintenance of C. elegans body wall muscle

“…unc-96 and unc-98 mutants are slower moving than wild type, and by polarized light microscopy display a moderately disorganized myofilament lattice and birefringent "needle-like" structures at the ends of their body wall muscle cells. These "needles" correspond to accumulations of proteins that contain paramyosin, but not actin, myosin, UNC-89, or α-actinin (Mercer et al, 2003;Mercer et al, 2006;. UNC-98 is a 310-residue polypeptide containing four C2H2 Zn finger domains and several predicted nuclear localization and nuclear export signal sequences (NLS and NES) (Mercer et al, 2003).…”

“…These "needles" correspond to accumulations of proteins that contain paramyosin, but not actin, myosin, UNC-89, or α-actinin (Mercer et al, 2003;Mercer et al, 2006;. UNC-98 is a 310-residue polypeptide containing four C2H2 Zn finger domains and several predicted nuclear localization and nuclear export signal sequences (NLS and NES) (Mercer et al, 2003). Antibodies to UNC-98 localize to M-lines.…”

Obscure functions: the location–function relationship of obscurins

“…Within the sarcomere at the level of the M-band, mammalian obscurins interact with titin, myomesin, ankyrin-B, Ras homolog gene family, member A (RhoA), and slow skeletal myosin binding protein C variant 1 (sMyBP-Cv1) (Perry et al 2013). In C. elegans at the M-band, UNC-89 interacts with copine domain protein atypical-1 (CPNA-1), UNC-15 (paramyosin), small CTD-phosphatase-like-1 (SCPL-1), four and a half LIM domains protein 9 (LIM9/FHL), maternal effect lethal 26 (MEL-26), and Rho1 (Gieseler et al 2016;Qadota et al 2008a, b;Warner et al 2013;Wilson et al 2012) and Drosophila obscurins interact with Ball and multiple ankyrin repeats single KH domain (MASK) at the M-band (Katzemich et al 2015). In addition, mammalian obscurins interact with the NH 2 -terminus of titin and Ran-binding protein 9 (RanBP9) at Z-discs (Bowman et al 2008), small ankyrin-1 at the SR , and ankyrin-B at costameres (Randazzo et al 2013).…”

“…Also unique to C. elegans, the NH 2 -terminus and kinase regions of UNC-89 interact with MEL-26 at sarcomeric M-bands (Wilson et al 2012). MEL-26 is a substrate recognition protein for cullin-3, an E3 ubiquitin ligase that is necessary for the assembly of the ubiquitin protein degradation machinery (Wilson et al 2012).…”

“…MEL-26 is a substrate recognition protein for cullin-3, an E3 ubiquitin ligase that is necessary for the assembly of the ubiquitin protein degradation machinery (Wilson et al 2012). The interaction of UNC-89 with MEL-26 likely provides a docking site, thereby mediating the regulation of protein turnover.…”