Challenging research

The biology of auxin action has enjoyed its share of controversy over the past century of research, from the mechanisms of its synthesis and distribution within the plant to questions around auxin-binding proteins, differences in concentration, and in sensitivities to the hormone. In recent years, some controversies have fuelled pseudoscientific theories that are roundly debunked within the core of the plant science community and beyond (Alpi et al., 2007; Taiz et al., 2019; Markel, 2020) but nonetheless have found their way into the popular press (Pollan 2013; Sample 2019; Rivera-Serrano 2021). Even without these perceptions to muddy the waters, there remains much that still requires clarity and challenges research.

In this issue of Plant Physiology, readers will find an article and two commentaries that mark an important step in this direction. Narasimhan et al. (2021) reassess the impact of the plant hormone auxin on membrane vesicle traffic and the underlying explanations for auxin action in regulating its own transport via PIN proteins. Their findings highlight a selective promotion of PIN turnover with no effect on PIN1 endocytosis, which on balance enhances the population of PIN proteins and auxin transport across the plasma membrane. They also report differences in the sensitivity of traffic to the natural auxin IAA and to the synthetic auxin NAA, the latter impacting on the pharmacokinetics of Brefeldin A that has long been used in studies of secretory traffic through the endoplasmic reticulum and Golgi to the plasma membrane. These findings certainly raise questions about pharmacological coapplications and their interpretation, although such concerns are by no means new to cell biologists.

More important, this study represents a volte face from work published some 15 years ago by the same laboratory that set the stage for much research that followed on in work with PIN proteins, vesicle traffic, and auxin cell biology (Paciorek et al., 2005; Dhonukshe et al., 2007). The essence of this earlier research was the claim that auxin acted to enhance the population of the PIN auxin efflux transporters at the plasma membrane by inhibiting their endocytosis. The reassessment by Narasimhan et al. (2021) is belated in as much as substantial evidence has continued to mount (Jasik and Schmelzer, 2014; Jasik et al., 2016; Paponov et al., 2019) that undermines several of the original assumptions and interpretations. Narasimhan et al. provide further temporal data, based on TIRF, confirming that IAA does not inhibit endocytosis per se but selectively promotes PIN2 recycling from the plasma membrane.

The two commentaries (Schwechheimer et al. 2021; Ten Tusscher 2021), published together with Narasimhan et al. (2021), revisit some of the detail behind the later studies and their implications for auxin-associated vesicle traffic in models of plant development. The commentaries will be helpful for readers less familiar with the controversy and its background. They also lay down challenges for us as scientists that are relevant, not only to the spheres of membrane traffic and auxin biology, but also to the way research is approached generally. In this era of large data and quantitative methods, or at least their “rediscovery,” there is all the more need for a healthy degree of skepticism (Bergstrom and West, 2021) and an awareness of the power of empirical falsification (in the sense of Karl Popper). These challenges apply equally in computational approaches to biology. To expand on Ten Tusscher (2021) and her reminder that mathematical models are never more than approximations to reality, let me add that models are valuable only to the extent that they allow us to interpret and, more still, to direct research and predict experimental outcomes. These are the true challenges of research.