Post-translational modification and regulation of actin

Abstract

Many of the best-studied actin regulatory proteins use non-covalent means to modulate the properties of actin. Yet, actin is also susceptible to covalent modifications of its amino acids. Recent work is increasingly revealing that actin processing and its covalent modifications regulate important cellular processes. In addition, numerous pathogens express enzymes that specifically use actin as a substrate to regulate their hosts cells. Actin post-translational alterations have been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight specific co- and post-translational modifications of actin and discuss the role that these modifications play in regulating actin dynamics.

Selenoproteins: Molecular Pathways and Physiological Roles

“…Moreover, oxidation of methionine residues has been shown to activate calcium/calmodulin (Ca 2ϩ /CaM)-dependent protein kinase II (CaMKII) in the absence of Ca 2ϩ /CaM, whereas MsrA activity could reverse this effect (93). Methionine oxidation has also been shown to regulate actin assembly by inhibiting formation of F-actin filaments (342). Remarkably, oxidation of the methio-nine residues in actin occurs through a targeted enzymebased modification rather than through nonspecific oxidation by ROS.…”

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

“…DAAM (DAAM1 in mammals) is one of four Drosophila formins (Diaphanous, DAAM, Fhos and CG32138) reported to be present in the nervous system (Pawson et al, 2008;Prokop et al, 2011;Sánchez-Soriano et al, 2007). DAAM has now been shown to be the essential formin in growth cones of embryonic neurons, where it promotes filopodia formation and axonal pathfinding in As described by Janke and Bulinski, 2011;Terman and Kashina, 2013. Cytoskeletal machinery of neurons 2335 the central nervous system (CNS) Matusek et al, 2008). Psidin (known as NAA25 in mammals) is the auxiliary subunit of the NatB acetylation complex required for protein acetylation (Stephan et al, 2012).…”

“…Both have in common that they are polymers of repetitive building blocks (black helmet-like symbols in the figure) that are assembled in a polar fashion. Their dynamics are regulated in comparable ways through the following different classes of actin-binding proteins (ABPs) and MT-binding proteins (MTBPs) as illustrated in the box figure. (1) New actin filaments or MTs are generated through nucleation factors that catalyse the transition from mono-or oligomers to polymers; (2) plus-end dynamics, such as (de-)polymerisation, stabilisation, directionality and targeting is regulated by plus-endbinding proteins; (3) nucleation or (de-)polymerisation processes are further regulated by proteins that bind actin or tubulin monomers or oligomers and determine their availability, for example, SCAR or N-WASP activates Arp2/3 nucleation, APC1 cooperates with mDia1 in nucleation, stathmin sequesters tubulin, profilin enhances actin polymerisation by ENAH (Bear and Gertler, 2009;Okada et al, 2010;Pollitt and Insall, 2009;Steinmetz, 2007); (4) proteins that bind along actin filaments or MTs can stabilise them against depolymerisation, cross-link them into bundles and/or networks, and/or link them to other cytoskeletal components, organelles or the cortex; (5) minus-end-binding proteins regulate stability versus (de-)polymerisation; (6,7) plusand minus-end-directed motor proteins mediate filament contraction, the sliding along other cellular structures or filaments, or the transport of cargo (C in the figure) along F-actin or MTs; (8) different classes of proteins can sever or actively depolymerise F-actin or MTs, for example, cofilin depolymerises or severs pointed ends of F-actin, type 13 kinesins depolymerise MTs from the plus end, and katanin or spastin sever MT shafts (Pak et al, 2008;Conde and Cá ceres, 2009); (9) post-translational modifications (PTM) influence F-actin or MT stability and the interaction with certain ABPs and MTBPs (Fukushima et al, 2009;Janke and Bulinski, 2011;Terman and Kashina, 2013). The importance and challenge of understanding cytoskeletal machinery Clearly, the cytoskeleton has essential roles during axonal growth, but we still do not understand how it is regulated to perform these functions.…”

Contribution of NADPH-oxidase to the establishment of hippocampal neuronal polarity in culture

“…Thus, Rac1 and Cdc42, members of the small GTPase Rho family, promote neuronal polarization and axonal growth (Gonzalez-Billault et al, 2012). Oxidation of actin decreases its ability to polymerize (Hung et al, 2011(Hung et al, , 2010Sakai et al, 2012;Terman and Kashina, 2013). However, inhibition of NOX reduces both the F-actin content at the growth cone and the retrograde actin flow in neurons, suggesting a crosslink between NOX and actin dynamics (Munnamalai and Suter, 2009;Munnamalai et al, 2014).…”