Sortinl

The protein secretion was dramatically reduced with increased Sortinl, which indicates that it might cause lethality at higher dosage. 

Six strong Sortinl hypersensitive (slh) Arabidopsis mutants were identified after three rounds of screens [9]. 

Sortinl-Hypersensitive Mutants Link Vacuolar Trafficking to Flavonoids Metabolism... 

Figure 19.2 Sortinl affects flavonoid transport to the vacuole, (a) Seed coat colors of different slh mutants, (b) DMACA staining shows that some slh mutants (2-50, 2-21, and 10-27) have defects in vacuolar accumulation of proanthocyanidins in the seed coats, (c-e) The recessive mutant slh2-50 is allelic to tt4, a flavonoid biosynthesis mutant that also affects vacuole morphology. The localization of EGFP-5TIP in...

It was also noticed that Sortinl is not stable in Arabidopsis growth media and probably decomposes to produce a compound that is active [9]. The authors analyzed different Sortinl substructures for their induction of vacuolar morphology and anthocyanin vacuolar accumulation defects [9]. It was found that the substructure in Figure 19.3j is required for induction of vacuolar morphology defects and the substructure in Figure 19.3k is required for the induction of the anthocyanin vacuolar accumulation defect. 

Figure 19.3 Sortinl-induced phenotypes resemble those of the glutathione biosynthesis inhibitor BSO. (a-c) Both Sortin 1 (b) and BSO (c) inhibit root hair elongation compared with the control (a), (d-f) Fluorescence accumulation in neutral red staining bodies in untreated (d), Sortin 1-treated (e), or BSO-treated (f) seedlings. The seedlings were grown under AlC conditions and stained with Naringenin. The samples were excited with a 543 nm laser line and the fluorescence was detected in the 565-620nm range, (g-i) Both Sortini...

Sortinl Disrupts Vacuolar Trafficking of both Proteins and Flavonoids... 

Sortinl affects the vacuolar trafficking of both proteins and flavonoids, indicating that flavonoid transport to the vacuole could share the same membrane-mediated pathway as vacuolar proteins. But this does not rule out the possibility that one of the trafficking defects is direct, whereas the other one is indirect. The fact that Sortinl mimics BSO to produce an oxidized cell environment to affect ABC transporter activity supports a model that a transporter-mediated flavonoid transport defect induces miss-trafficking of other vacuolar contents such as the proteins. On the other hand, mutants defective in flavonoid metabolism, such as tt4, show hypersensitivity to Sortinl and have altered vacuolar morphology... 

Sortinl decomposes in plant growth media where one of the products resembles the effects of BSO, a GSH biosynthesis inhibitor. This indicates that a series of observed Sortinl effects might be due to an oxidized cellular environment that it creates. It could be that Sortinl or an active decomposition product sequesters GSH or inhibits GSH production. This may induce the transcription of cytochrome P450-dependent monooxygenases and mixed function oxidases, as shown in the transcription profile after Sortinl treatment. Reduced GSH level then affects flavonoid transport. 

As reported by Rosado and coworkers [9], not all the slh mutants have flavonoid accumulation/transport defects this indicates that there are flavonoid-independent pathways that involve the regulation Sortinl-targeted vacuolar... 

Sortinl-hypersensitive mutants link vacuolar-trafficking defects and flavonoid metabolism in Arabidopsis vegetative tissues, Chem. Biol, 18, 187-197. 

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