Diversity and evolution of actin-dependent phenotypes
Section snippets
Complex regulation underlies actin phenotype diversity
Actin is among the most abundant proteins in eukaryotic cells and is often maintained at concentrations in excess of 200 μM [1]. At such high concentrations, actin monomers readily assemble into dynamic polymers. To avoid becoming a solid brick of polymerized actin, a cell must maintain tight control over its actin monomer pool (Figure 1). This control is mediated by a dizzying and ever-growing list of molecular regulators, including monomer-binding proteins that suppress spontaneous actin
The pre-eukaryotic origins of actin
The ubiquity of phenotypes that are controlled by actin raises a seemingly simple question: ‘Where did actin come from?’ The discovery of actin structural homologs in bacteria, and more recently in archaea, indicates that actin-like polymers are used by cells across the tree of life. These proteins are commonly referred to as ‘actins’ despite no obvious sequence homology to eukaryotic actin, raising the possibility that this term may carry eukaryotic connotations that are misleading.
The genetic
Tracing the evolution of complex actin networks
Actin coordinates almost all cellular activities, and homologs of its major regulators have been identified in nearly every eukaryotic species. Phylogenetic analyses indicate that profilin [44], formins [45,46], the Arp2/3 complex and its upstream activators [47,48], major classes of myosin motors [49], and various other actin regulators were most likely present in the genome of the last common eukaryotic ancestor. However, the presence of an individual actin binding protein does not tell much
Leveraging eukaryotic diversity to understand actin cytoskeletal phenotypes
A major bottleneck to understanding actin-dependent phenotypes is the complexity of the actin cytoskeleton at every level (Figure 1). At the sequence level, eukaryotes often have multiple actin isoforms. At the structural level, actin functions both as a monomer and as a polymer with diverse network architectures, with each network controlled by a wide variety of regulators. At the cellular level, actin monomers and networks interface with nearly every other cell system, particularly membranes,
Moving forward: using discovery-based science to shed light on ‘dark’ actin biology
Most of what we know about actin comes from studying a handful of genetically tractable species, most of which belong to a single major eukaryotic group: the opisthokonts. This group encompasses animals, fungi, and related organisms, leaving entire major eukaryotic groups with nearly no experimental data, especially regarding the actin cytoskeleton (Figure 4b). Because of the massive numbers of genes gained and lost by major eukaryotic groups [71], there undoubtedly remain important and
Outlook and conclusions
The broad conservation of actin and actin binding proteins highlights their importance to cell biology. Much of our understanding of the evolution of the behaviors encoded by actin networks, however, relies on the assumption that their biochemistry, network properties, and higher-level phenotypes are all conserved. Given the billions of years of evolution separating the major eukaryotic lineages, it is almost certain that actin-dependent phenotypes have diverged at least to some level. A
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Alison Wirshing (Brandeis University), Samantha Dundon (Yale), Alexander Paredez (University of Washington), Evan Craig (University of Kansas Medical Center), Aoife Heaslip (University of Connecticut), Michelle Facette (University of Massachusetts, Amherst), Qiong Nan (University of Massachusetts, Amherst), and Clinton Parraga (University of Connecticut) for providing images. We also thank Kenneth Campellone (University of Connecticut), Alison Wirshing, Bruce Goode (Brandeis
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