Oscillatory fungal cell growth

Abstract

Cells are dynamic systems, the state of which undergoes constant alteration that results in morphological changes and movement. Many dynamic cellular processes that appear continuous are driven by underlying mechanisms that oscillate with distinct periods. For example eukaryotic cells do not grow continuously, but rather by pulsed extension of the periphery. Stepwise cell extension at the hyphal tips of several filamentous fungi was discovered 20 years ago, but only a few molecular details of the mechanism have been clarified since then. A recent study has provided evidence for correlations among intracellular Ca²⁺ levels, actin assembly, exocytosis and cell extension in growing hyphal tips. This suggests that pulsed Ca²⁺ influxes coordinate the temporal control of actin assembly and exocytosis, which results in stepwise cell extension. The coordinated oscillation of these machineries are likely to be ubiquitous among all eukaryotes. Indeed, intracellular Ca²⁺ levels and/or actin polymerization oscillate in mammalian and plant cells. This review summarizes the mechanisms of oscillation in several systems.

Introduction

Filamentous fungi grow as highly polarized tubular cells called hyphae, that extend the cell body at one end in a process called “tip growth”. Cell extension sites are maintained at hyphal tips, where simultaneous actin assembly, exocytosis and tip extension occur (Fischer et al., 2008, Riquelme et al., 2011, Takeshita et al., 2014). Several filamentous fungi that extend cells in this manner are excellent systems for analyzing this process (Lopez-Franco et al., 1994). Some filamentous fungi are pathogenic to animals and plants and invade host cells via hyphal growth (Perez-Nadales et al., 2014). Others have uses in biotechnology and food production such as enzyme production and fermentation, respectively, as they secrete large amounts of enzymes (Kobayashi et al., 2007, Punt et al., 2002). Both the pathogenicity and enzyme secretory ability of fungi are closely associated with hyphal growth. Thus, understanding polarized growth in filamentous fungi can provide insights that are important to medicine, agriculture and biotechnology.

The extension of hyphal tips requires constant enlargement of the cell membrane. Vesicle trafficking supplies the required proteins and lipids via actin, as well as microtubule cytoskeletons and their corresponding motor proteins (Egan et al., 2012, Penalva et al., 2017, Steinberg, 2011, Taheri-Talesh et al., 2008). Microtubules serve as tracks of secretory vesicles for long-distance transport to hyphal tips and are important for rapid hyphal growth (Horio and Oakley, 2005, Seiler et al., 1997). Actin cables formed from the hyphal tip in the retrograde direction are involved in exocytosis and secretory vesicle accumulation before exocytosis (Berepiki et al., 2011, Bergs et al., 2016). Secretory vesicles accumulate and then secretion results in the formation of a fungal-specific structure, called the Spitzenkörper (Harris et al., 2005, Riquelme and Sanchez-Leon, 2014).

Besides their role as tracks for vesicle traffic, microtubules are necessary to maintain the direction of hyphal growth (Riquelme et al., 1998). Polar organization of the actin cytoskeleton is mediated mainly by microtubule-dependent positioning of polarity marker proteins. One polarity marker in Aspergillus nidulans (TeaA) is specifically delivered to the apex by growing microtubules, and it is anchored to the apical membrane by direct interaction with another polarity marker (TeaR) at the plasma membrane (Fischer et al., 2008, Takeshita et al., 2008). Their interdependent interaction at the apical membrane initiates the recruitment of additional components including the formin which polymerizes actin cables for targeted cargo delivery. Defective polarity markers result in hyphae that are curved or zigzagged instead of straight.

Although the stepwise cell extension at hyphal tips of several filamentous fungi was discovered 20 years ago (Lopez-Franco et al., 1994), most of the molecular details of the mechanism have remained obscure.