Prions first caught the attention of scientists when it was
discovered these protein particles were responsible for infectious
neurodegenerative diseases, like Mad-Cow Disease and CJD, in humans and other
organismal groups. Prions are
self-perpetuating proteins with distinct functions regulated by their flexible
structure (Newby & Lindquist, 2013).
Aside from the tissue degradation caused by infectious prion forms,
normal prion proteins can act as “molecular memory” markers that allow for the
inheritance of new traits across cell divisions (Shorter & Lindquist, 2005). When a cell divides any changes made to the
chromatin are typically erased, so prions that act as templates to save these
changes enable external stimuli, like the environment, to impact the genetic
information of the cell.
Memory conservation using prions has been observed in
organisms from yeast to humans; however, plants were thought to record genetic
changes through epigenetic marks, a method independent of prion proteins, until
the work of Chakrabortee et al. (2016). Their
research aimed to identify prion-like domains (PrDs) within plant proteins and
associate them with prion memory behavior.
Over 500 Arabidopsis
plant proteins were identified as potential PrDs, but Chakrabortee et
al. (2016) narrowed their focus to three
PrDs that are involved in the flowering pathway. Prion-like domains were identified and scored
for similarity using a matching program that compared Arabidopsis protein
sequences to known yeast prion sequences.
Out of the 8 proteins involved in the Arabidopsis flowering
pathway, half were identified as PrDs - Luminidependens (LD), Flowering Locus
PA (FPA), Flowering Locus CA (FCA), and Flowering Locus Y (FY). Three of the Arabidopsis PrDs (LD,
FPA, and PA) were expressed in yeast, and they displayed similar
characteristics to yeast prions, such as foci fusion leading to one distinct
foci for each protein.
 |
Figure 1: Sup35 Assay with the flowering pathway
PrDs at low expression levels (left) and
over-expressed levels (right) on adenine-deficient
medium. Figure taken from Chakrabortee et al. 2016.
|
A defining feature
of prion proteins is their ability to continuously renew their structure to act
as a template converting normal proteins of a similar type to the prion form. To test this characteristic in the flowering
pathway PrDs, a Sup35 protein was expressed in cells with each of the PrDs to
determine if they influenced the function of this translational repressor
(Sup35). Normally Sup35 disrupts cell
growth by causing the ribosomes to stop translation at the ending stop codon
sequence; however, Sup35 bound to an active prion does not prevent ribosomes
from reading through the stop codon to continue translation (Cai et al., 2014). Only cells expressing the LD PrD were found
to have template-like behavior, as over-expressed LD led to continued cell
growth, when at lower levels of LD, Sup35 remained active and led to cell death
in absence of adenine (Figure 1). This data suggested
LD PrDs have strong prion-like characteristics.
The effects of LD
PrD were also observed to create heritable changes stabilized across several
generations of cell growth. Heritability
is key as it allows information to be recorded and passed along from one
generation to another. The direct
response of an organism to environmental changes can be retained using prion
memory behavior, thus allowing faster paced phenotypic change. With our environment changing more rapidly
than ever, prions and their molecular memory may be essential for species
survival (Figure 2).
 |
| Figure 2: Observed changes in flowering onset across the United States. Data from the Environmental Protection Agency marks advances and lapses in plant bloom time over two 9 year periods. Sustained differences in bloom time may indicate the role of a heritable, molecular memory mechanism for this trait. |
The discovery of a
plant protein with prion behavior is entirely new to the field of prion
research. The LD protein, which is part
of the flowering pathway, clearly shows prion-like behavior in both structure
and function. The next step is to look
for an association between changes in flowering patterns and LD structural
changes to understand the role this PrD has in the Arabidopsis life
cycle. Plant memory mechanisms are still
largely unknown, so these findings may help to explain how external stimuli can
impact the chromatin in certain ways, following certain events. This field therefore holds a great deal of
potential for molecular biologists and conservation research focusing on phenotypic
plant variation.
Chakrabortee, Sohini, Can Kayatekin, Greg A. Newby, Marc L. Mendillo, Alex Lancaster, and Susan Lindquist. "Luminidependens (LD) is an Arabidopsis protein with prion behavior." Proceedings of the National Academy of Sciences (2016): 201604478.
Cai, Xin, Jueqi Chen, Hui Xu, Siqi Liu, Qiu-Xing Jiang,
Randal Halfmann, and Zhijian J. Chen. "Prion-like polymerization underlies
signal transduction in antiviral immune defense and inflammasome
activation." Cell 156.6 (2014): 1207-1222.
Newby, Gregory A., and Susan Lindquist. "Blessings in
disguise: biological benefits of prion-like mechanisms." Trends in
cell biology 23.6 (2013): 251-259.
Shorter, James, and Susan Lindquist. "Prions as
adaptive conduits of memory and inheritance." Nature Reviews
Genetics 6.6 (2005): 435-450.
Figures:
Figure 1 - Data taken from figure 2A (Chakrabortee et al., 2016)
Figure 2 - Data from the EPA on flower bloom time - https://www.epa.gov/climate-indicators/climate-change-indicators-leaf-and-bloom-dates
