Myosin light chains: Teaching old dogs new tricks

Abstract

The myosin holoenzyme is a multimeric protein complex consisting of heavy chains and light chains. Myosin light chains are calmodulin family members which are crucially involved in the mechanoenzymatic function of the myosin holoenzyme. This review examines the diversity of light chains within the myosin superfamily, discusses interactions between the light chain and the myosin heavy chain as well as regulatory and structural functions of the light chain as a subunit of the myosin holoenzyme. It covers aspects of the myosin light chain in the localization of the myosin holoenzyme, protein-protein interactions and light chain binding to non-myosin binding partners. Finally, this review challenges the dogma that myosin regulatory and essential light chain exclusively associate with conventional myosin heavy chains while unconventional myosin heavy chains usually associate with calmodulin.

Various Themes of Myosin Regulation

“…Large structural and functional diversification is found in myosin non-motor domains: The neck domain typically contains one to six IQ motifs in vertebrate myosins which non-covalently associate with a specific set of calmodulin-like light chains [11]. Tail domains are most diverse and constitute a regulatory hotspot of the holoenzyme due to a vast domain complement including coiled-coils that mediate oligomerization, my osin t ail h omology; f ourpoint-one, e zrin, r adixin, m oesin (MyTH/FERM) and pleckstrin homology (PH) domains that mediate the interaction with binding partners and phosphoinositides (PtdIns).…”

“…Strikingly, kinetic and functional studies of phosphomimetic mutants exclude TEDS-phosphorylation as a major regulatory mechanism in vitro, though cellular studies suggest phosphorylation-dependent myosin-6:actin interactions [72–74]. A possible explanation for discrepancy may be the use of phosphomimetic myosin mutants that do not always mimic bona fide phosphorylation [11, 75]. …”

“…The effect of both, free Ca 2+ and Mg 2+ on the myosin holoenzyme is multimodal and either direct or indirect via interactions with the myosin heavy chain or the associated light chains [11]. Most identified myosin light chains have 4 EF-hand domains that may bind Ca 2+ and/or Mg 2+ .…”

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure

“…Thus, to analyse the contribution of Myosin phosphorylation to Myosin foci dynamics, we used GFP-tagged forms of Sqh phosphomutants affecting serine 21 only, under the control of the sqh promoter (Vasquez et al, 2014). Although biochemical studies have raised some caveats for the use of these mutant variants (Heissler and Sellers, 2015), in vivo studies have shown that substitution of serine 21 by alanine (SqhA21) or by glutamate (SqhE21) decrease or increase, respectively, Myosin activity (Heissler and Sellers, 2015;Jordan and Karess, 1997;Kasza et al, 2014;Vasquez et al, 2014). To reduce endogenous Sqh levels, we combined Sqh phosphomutants with a hypomorphic sqh 1 mutant allele.…”

Drosophila non-muscle myosin II motor activity determines the rate of tissue folding

“…The motor domain catalyzes the hydrolysis of ATP to power the translocation of actin filaments, a function referred to as motor activity. The light chains bind to the central neck domain of the myosin heavy chain and have structural and regulatory functions (Heissler and Sellers, 2014). The C-terminal tail of the myosin heavy chain associates with the tails of other myosin heavy chains and promotes the assembly into bipolar filaments.…”