A Conditional Mutation in SCD1 Reveals Linkage Between PIN Protein Trafficking, Auxin Transport, Gravitropism, and Lateral Root Initiation.

Auxin is transported in plants with distinct polarity, defined by transport proteins of the PIN-formed (PIN) family. Components of the complex trafficking machinery responsible for polar PIN protein localization have been identified by genetic approaches, but severe developmental phenotypes of trafficking mutants complicate dissection of this pathway. We utilized a temperature sensitive allele of Arabidopsis thaliana SCD1 (stomatal cytokinesis defective1) that encodes a RAB-guanine nucleotide exchange factor. Auxin transport, lateral root initiation, asymmetric auxin-induced gene expression after gravitropic reorientation, and differential gravitropic growth were reduced in the roots of the scd1-1 mutant relative to wild type at the restrictive temperature of 25°C, but not at the permissive temperature of 18°C. In scd1-1 at 25°C, PIN1- and PIN2-GFP accumulated in endomembrane bodies. Transition of seedlings from 18 to 25°C for as little as 20 min resulted in the accumulation of PIN2-GFP in endomembranes, while gravitropism and root developmental defects were not detected until hours after transition to the non-permissive temperature. The endomembrane compartments that accumulated PIN2-GFP in scd1-1 exhibited FM4-64 signal colocalized with ARA7 and ARA6 fluorescent marker proteins, consistent with PIN2 accumulation in the late or multivesicular endosome. These experiments illustrate the power of using a temperature sensitive mutation in the gene encoding SCD1 to study the trafficking of PIN2 between the endosome and the plasma membrane. Using the conditional feature of this mutation, we show that altered trafficking of PIN2 precedes altered auxin transport and defects in gravitropism and lateral root development in this mutant upon transition to the restrictive temperature.

Adenotonsillectomy outcomes in patients with Down syndrome and obstructive sleep apnea.

OBJECTIVE: To review the literature for studies examining polysomnography (PSG) outcomes in patients with Down syndrome (DS) and obstructive sleep apnea (OSA) following adenotonsillectomy (T&A), and to review our experience with these patients. DATA SOURCES: PubMed-NCBI, Scopus, Ovid, EBSCO, Cochrane, and EMBASE databases; tertiary academic center medical records. REVIEW METHODS: A systematic review of the medical literature identified articles reporting objective outcomes following T&A for OSA treatment in patients with DS. Articles were critically appraised to assess level of evidence and bias, and the results of articles were summarized. A case series of confirmed patients with DS and OSA was conducted, evaluating T&A efficacy by comparing pre- and posttreatment PSG data. RESULTS: Six articles were identified, which demonstrated some improvement after T&A in the treatment of OSA; however, subjects frequently had persistent disease. At our institution, preoperative Apnea-Hypopnea Index (AHI) improved from 13.75 (interquartile range [IQR] = 6.65-23.43) to 3.5 (IQR = 1.96-9.63) postoperatively; P = 0.004. Ten percent of patients had preoperative AHIs < 5; this proportion increased to 60% following surgery. Twenty percent of patients had postoperative AHIs < 1. CONCLUSION: There is little objective data in the medical literature addressing T&A efficacy in treating OSA in patients with DS patients. Patients show objective improvement in sleep parameters following T&A for OSA. Adenotonsillectomy should be suggested as a first-line treatment for children with DS and OSA, keeping in mind that monotherapy may be insufficient. Future studies utilizing objective measures are required to further quantify the effect in this patient population. LEVEL OF EVIDENCE: Laryngoscope, 127:1465-1470, 2017.

Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis.

The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells and enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. This study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease.