Life as a moving fluid: fate of cytoplasmic macromolecules in dynamic fungal syncytia

doi:10.1016/j.mib.2015.07.001

Current Opinion in Microbiology

Volume 26, August 2015, Pages 116-122

https://doi.org/10.1016/j.mib.2015.07.001 Get rights and content

Highlights

•
Fungal syncytia are models for the study of functional compartmentalization of cells.
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Diffusion, cytoplasmic flow and degradation determine how far each macromolecule disperses.
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Localization of macromolecules can be predicted by physical modeling.
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Aggregation, corralling, septa and shear set localization distances.
•
Multinucleate organization is shaped by localization and dispersion of macromolecules.

In fungal syncytia dozens, or even millions of nuclei may coexist in a single connected cytoplasm. Recent discoveries have exposed some of the adaptations that enable fungi to marshall these nuclei to produce complex coordinated behaviors, including cell growth, nuclear division, secretion and communication. In addition to shedding light on the principles by which syncytia (including embryos and osteoplasts) are organized, fungal adaptations for dealing with internal genetic diversity and physically dynamic cytoplasm may provide mechanistic insights into how cells generally are carved into different functional compartments. In this review we focus on enumerating the physical constraints associated with maintaining macromolecular distributions within a fluctuating and often flowing cytoplasmic interior.

Introduction

Biomechanicians have studied extensively the adaptations that enable organisms including plants, insects, larvae and bacteria, to deal with external fluid flows, from wind to water currents in rivers and the ocean [1]. However cells encounter a parallel challenge of creating and shaping internal flows. Filamentous fungi have especially dynamic cellular interiors: in Neurospora crassa mycelia continuous transport of cytoplasm from the mycelial interior to its growing edges carries nuclei, cytoplasm and organelles at speeds of 10s of microns per second [2]. Even in slower growing fungi nuclei and organelles may be in constant motion [3, 4]. Although these flows allow long range transport of nutrients and organelles over the colony, mechanisms are needed to localize the mRNAs and proteins that direct spatially regulated processes, for example, cytokinesis [5] or cell–cell communication [6]. In this review we will highlight primarily the role of physical mechanisms that allow ascomycete fungi to localize macromolecules against both diffusion and cytoplasmic flow. We will also discuss how mRNA and protein homogenization between may allow the fungus to tolerate internal genetic and epigenetic diversity. Increasing data suggests that these cellular-level dynamics are a motor for virulence and for the ability of the fungus to adapt to new hosts and changing environments.

Section snippets

Fungal models for dynamic syncytia

In this review we focus on filamentous ascomycete fungi. There are multiple reasons for choosing filamentous fungi as syncytial models: first, fungal compartments are among the largest of syncytia, capable of forming cytoplasmically connected networks that extend several centimeters [7^•]. Second, transport within these networks is associated with rapid and long-ranged cytoplasmic flow. For example single nuclei may travel several centimeters through a N. crassa mycelium [8^•] at speeds of up to

Physical mechanisms for the localization of proteins and mRNAs within the fungal syncytium

Proteins and mRNAs may travel through a continuous cytoplasm either by diffusion or by flow. In common with other cells [20, 21•], filamentous fungi use active transport along the cytoskeleton to localize some mRNAs, for example those associated with polarity establishment [22]. For some proteins (e.g., the protein-rich Spitzenkörper at growing hyphal tips [3]) localization seems to involve protein-cell membrane interactions. However for many macromolecules there is no known cytoskeletal

Discussion — an heterogeneous or homogeneous cellular interior?

We have physically organized the known adaptations used by fungi to localize macromolecules at specific points in the cell and highlighted evidence that these macromolecules are controllably and heterogeneously patterned through the syncytium. At the same time, dispersal of macromolecules through a shared cytoplasm endows fungi with tolerance for internal genetic diversity [7^•]. In addition to providing a source of phenotypic plasticity [17^•], shielding of deleterious mutations may facilitate

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest

Acknowledgements

MR and PCH are supported by the NSF (DMS-1351860) and the Alfred P. Sloan Foundation. ASG is supported by the NIH (NIGMS R01GM081506) and the NSF (MCB-507511).

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Bursty transcription allows nuclei to concentrate the work of transcribing mRNA into short, intermittent intervals, potentially reducing transcriptional interference. However, bursts of mRNA production can increase noise in protein abundances. Here, we formulate models for gene expression in syncytia, or multinucleate cells, showing that protein abundance noise may be mitigated locally via spatial averaging of diffuse proteins. Our modeling shows a universal reduction in protein noise, which increases with the average number of nuclei per cell and persists even when the number of nuclei is itself a random variable. Experimental data comparing distributions of a cyclin mRNA that is conserved between brewer’s yeast and a closely related filamentous fungus Ashbya gossypii confirm that syncytism is permissive of greater levels of transcriptional noise. Our findings suggest that division of transcriptional labor between nuclei allows syncytia to sidestep tradeoffs between efficiency and precision of gene expression.
Cellular communication and fusion regulate cell fusion, trap morphogenesis, conidiation, and secondary metabolism in Arthrobotrys oligospora
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Signal-mediated cell fusion is vital for colony development in filamentous fungi. Arthrobotrys oligospora is a representative nematode-trapping (NT) fungus that produces adhesive networks (traps) to capture nematodes. Here, we characterized Aoadv-1, Aoso, Aoham-6, and Aoham-5 of A. oligospora, homologs of proteins involved in cellular communication and fusion in the model fungus Neurospora crassa. The deletion of four genes resulted in the complete loss of cell fusion, and traps produced by mutants did not close to form mycelial rings but were still capable of capturing nematodes. The absence of these genes inhibits aerial mycelial extension, slows colony growth, and increases mycelial branching. In addition, the mutants showed reduced sporulation capacity and tolerance to oxidative stress, increased sensitivity to SDS, and disturbed lipid droplet accumulation and autophagy. In addition, transcriptome and metabolomic analyses suggested that Aoadv-1 and Aoso are involved in multiple cellular processes and secondary metabolism. Our results revealed that Aoadv-1, Aoso, Aoham-6, and Aoham-5 regulate mycelial growth and trap morphogenesis through cell fusion, which contributed to elucidating the molecular mechanisms of cellular communication regulating mycelial development and trap morphogenesis in NT fungi.
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Hyphae can be divided into cellular compartments by regularly deposited septa. In the multicellular fungi (Pezizomycotina in the Ascomycota, and Agaricomycotina in the Basidiomycota), septa typically possess a central pore, which is sufficiently large to allow the passage of organelles and bulk protoplasmic flow.2,6,7 This aids younger hyphae in their growth.
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Subcellular localization of mRNAs is known to be crucial to a variety of cellular functions including cell cycle regulation and proper development in many organisms [1–12].
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View full text

Life as a moving fluid: fate of cytoplasmic macromolecules in dynamic fungal syncytia

Highlights

Introduction

Section snippets

Fungal models for dynamic syncytia

Physical mechanisms for the localization of proteins and mRNAs within the fungal syncytium

Discussion — an heterogeneous or homogeneous cellular interior?

References and recommended reading

Acknowledgements

Fungal Genet Biol

Curr Opin Microbiol

Curr Biol

Development

Proc R Soc B

Eukaryot Cell

RNA Biol

Curr Biol

Genes Dev

Cell

Rev Mod Phys

Microbiology

Biosci Biotechnol Biochem

mBio

Life in Moving Fluids: The Physical Biology of Flow

Mass flow and pressure-driven hyphal extension in Neurospora crassa

Microbiology

Hyphal growth: a tale of motors, lipids, and the Spitzenkörper

Eukaryot Cell

Mobility, microtubule nucleation and structure of microtubule-organizing centers in multinucleated hyphae of Ashbya gossypii

Mol Biol Cell

Nuclear dynamics in a fungal chimera

Proc Natl Acad Sci U S A

Nuclear behavior in fungal hyphae

FEMS Microbiol Lett

How an actin network might cause fountain streaming and nuclear migration in the syncytial Drosophila embryo

J Cell Biol

Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo

J Cell Biol

Nucelo-cytoplasmic interactions in the achievement of nuclear synchrony in DNA synthesis and mitosis in multinucleate cells

Biol Rev

The DNA damage checkpoint signal in budding yeast is nuclear limited

Mol Cell

A conserved G1 regulatory circuit promotes asynchronous behavior of nuclei sharing a common cytoplasm

Cell Cycle

Nuclear repulsion enables division autonomy in a single cytoplasm

Curr Biol

Protein aggregation behavior regulates cyclin transcript localization and cell-cycle control

Dev Cell