Sphingolipids and plant defense/disease: the "death" connection and beyond

Abstract

Sphingolipids comprise a major class of structural materials and lipid signaling molecules in all eukaryotic cells. Over the past two decades, there has been a phenomenal growth in the study of sphingolipids (i.e., sphingobiology) at an average rate of ∼1000 research articles per year. Sphingolipid studies in plants, though accounting for only a small fraction (∼6%) of the total number of publications, have also enjoyed proportionally rapid growth in the past decade. Concomitant with the growth of sphingobiology, there has also been tremendous progress in our understanding of the molecular mechanisms of plant innate immunity. In this review, we (i) cross examine and analyze the major findings that establish and strengthen the intimate connections between sphingolipid metabolism and plant programmed cell death (PCD) associated with plant defense or disease; (ii) highlight and compare key bioactive sphingolipids involved in the regulation of plant PCD and possibly defense; (iii) discuss the potential role of sphingolipids in polarized membrane/protein trafficking and formation of lipid rafts as subdomains of cell membranes in relation to plant defense; and (iv) where possible, attempt to identify potential parallels for immunity-related mechanisms involving sphingolipids across kingdoms.

Keywords: Arabidopsis; defense; hypersensitive response; lipid raft; pathogen; polarized trafficking; programmed cell death; sphingolipid.

Figure 1

The basic structure, building blocks, and sources for structural diversity of sphingolipids. All the structural variables are highlighted in red and indicated by a number in a shaded circle. Ceramide (Cer) is the fundamental unit of all complex sphingolipids. The Cer core consists of two structural moieties: the sphingoid long-chain base (LCB) and the fatty acid (FA) chain linked via an amide bond. The typical LCB has a chain length of 18 carbons, which may be hydroxylated at 4-position➊, or have a double bond at the 4 or 8 carbon➋. The FA chain may be hydroxylated at the α-position➌, and/or have a double bond at ω9-position➍. The FA chain length may vary from 14 to 36 (if >20, it is referred to as very long-chain FA, i.e., VLCFA)➎. The structurally diverse ceramides can be converted to more complex sphingolipids via substitution of the head group designated R at the 1-position of the LCB➏. Additional sugar residues may be further added to IPCs and GlcCERs, resulting in more complex sphingolipids.

Figure 2

The major steps of sphingolipid metabolism in plants. De novo ceramide synthesis occurs in the ER and synthesis of more complex sphingolipids occurs in the Golgi apparatus. The metabolic steps genetically characterized to be critical for plant PCD regulation are enumerated ➊ to ➏; Name of enzymes are in white boxes, and genetically characterized ones in gray boxes; Uncharacterized steps are linked with dashed lines.

Figure 3

RPW8.2 may be targeted to and function at microdomains of the extrahaustorial membrane (EHM) in Arabidopsis. A confocal image from a Z-stack projection showing that RPW8.2:YFP (green) is initially found in discrete punctate spots in the EHM at ∼18 h after inoculation with powdery mildew before forming a relatively more homogenous distribution in the next 4–6 h (Wang et al., 2009). The fungal structure and the host plasma membrane are stained red by propidium iodide. H, haustorium; A, appressorium.

Figure 4

A cartoon summarizing the major connections between sphingolipids and plant immunity. (i) PAMP-triggered immunity (PTI) involves a MAPK signaling module; MPK6 as a component of PTI is targeted by a pathogen effector HopA1 presumably for suppressing PTI. (ii) Effector-triggered immunity may involve accumulation of sphingoid long-chain bases (LCBs; t18:0 in particular) from de novo synthesis as an early signaling step upstream of SA. (iii) MPK6 is a potential direct protein target of LCBs; Upon activation by LCBs, MPK6 functions to promote SA-dependent HR and defense against (hemi)-biotrophic pathogens, thereby bridging up ETI and PTI. (iv) Some necrotrophic pathogens secrete toxin AAL or FB1 to inhibit (VLCFA-)ceramide synthesis and cause accumulation of LCBs, which in turn may activate MPK6, resulting in plant PCD for the benefit of the pathogens. (v) Ceramides are synthesized at the ER, and transferred to the Golgi apparatus where they are converted to inositol-phosphorylceramides (IPCs), and/or more complex glycosphingolipids. Ceramide accumulation due to acd5 and erh1 mutations results in SA-dependent PCD, suggesting ceramides are essential signaling molecules for PCD. (vi) Glycosphingolipids (especially those containing VLCFAs) are sorted at the trans-Golgi into transport vesicles carrying relevant immune protein cargos (the FLS2 PAMP receptor and the RPW8 resistance protein as examples) to regulate specific targeting of cargos to specific cell membranes (the plasma membrane and the extrahaustorial membrane, respectively, in these two cases). (vi) Glycosphingolipids increase the molecular ordering of the cell membrane, forming microdomains (lipid rafts) that constitute lateral functional clusters in the cell membrane where plant immunity proteins may reside and function.