Predicted cellular role

Primary literature for the Solute_trans_a domain is listed below.

Lazarus1, a DUF300 protein, contributes to programmed cell death associated with Arabidopsis acd11 and the hypersensitive response.

Malinovsky FG, Brodersen P, Fiil BK, McKinney LV, Thorgrimsen S, Beck M, Nielsen HB, Pietra S, Zipfel C, Robatzek S, Petersen M, Hofius D, Mundy J
PLoS One. 2010; 5: 12586-12586

BACKGROUND: Programmed cell death (PCD) is a necessary part of the life ofmulti-cellular organisms. A type of plant PCD is the defensive hypersensitiveresponse (HR) elicited via recognition of a pathogen by host resistance (R)proteins. The lethal, recessive accelerated cell death 11 (acd11) mutant exhibitsHR-like accelerated cell death, and cell death execution in acd11 shares genetic requirements for HR execution triggered by one subclass of R proteins.METHODOLOGY/PRINCIPAL FINDINGS: To identify genes required for this PCD pathway, we conducted a genetic screen for suppressors of acd11, here called lazarus (laz)mutants. In addition to known suppressors of R protein-mediated HR, we isolated13 novel complementation groups of dominant and recessive laz mutants. Here wedescribe laz1, which encodes a protein with a domain of unknown function(DUF300), and demonstrate that LAZ1 contributes to HR PCD conditioned by theToll/interleukin-1 (TIR)-type R protein RPS4 and by the coiled-coil (CC)-type Rprotein RPM1. Using a yeast-based topology assay, we also provide evidence thatLAZ1 is a six transmembrane protein with structural similarities to the humantumor suppressor TMEM34. Finally, we demonstrate by transient expression ofreporter fusions in protoplasts that localization of LAZ1 is distributed between the cytosol, the plasma membrane and FM4-64 stained vesicles.CONCLUSIONS/SIGNIFICANCE: Our findings indicate that LAZ1 functions as aregulator or effector of plant PCD associated with the HR, in addition to itsrole in acd11-related death. Furthermore, the similar topology of a plant andhuman DUF300 proteins suggests similar functions in PCD across the eukaryotickingdoms, although a direct role for TMEM34 in cell death control remains to beestablished. Finally, the subcellular localization pattern of LAZ1 suggests that it may have transport functions for yet unknown, death-related signalingmolecules at the plasma membrane and/or endosomal compartments. In summary, ourresults validate the utility of the large-scale suppressor screen to identifynovel components with functions in plant PCD, which may also have implicationsfor deciphering cell death mechanisms in other organisms.

The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is anileal basolateral bile acid transporter.

Dawson PA, Hubbert M, Haywood J, Craddock AL, Zerangue N, Christian WV, Ballatori N
J Biol Chem. 2005; 280: 6960-8

Bile acids are transported across the ileal enterocyte brush border membrane bythe well characterized apical sodium-dependent bile acid transporter (Asbt)Slc10a2; however, the carrier(s) responsible for transporting bile acids acrossthe ileocyte basolateral membrane into the portal circulation have not been fullyidentified. Transcriptional profiling of wild type and Slc10a2 null mice wasemployed to identify a new candidate basolateral bile acid carrier, theheteromeric organic solute transporter (Ost)alpha-Ostbeta. By Northern blotanalysis, Ostalpha and Ostbeta mRNA was detected only in mouse kidney andintestine, mirroring the horizontal gradient of expression of Asbt in thegastrointestinal tract. Analysis of Ostalpha and Ostbeta protein expression byimmunohistochemistry localized both subunits to the basolateral surface of themouse ileal enterocyte. The transport properties of Ostalpha-Ostbeta wereanalyzed in stably transfected Madin-Darby canine kidney cells. Co-expression of mouse Ostalpha-Ostbeta, but not the individual subunits, stimulatedNa(+)-independent bile acid uptake and the apical-to-basolateral transport oftaurocholate. In contrast, basolateral-to-apical transport was not affected byOstalpha-Ostbeta expression. Co-expression of Ostalpha and Ostbeta was requiredto convert the Ostalpha subunit to a mature glycosylated endoglycosidaseH-resistant form, suggesting that co-expression facilitates the trafficking ofOstalpha through the Golgi apparatus. Immunolocalization studies showed thatco-expression was necessary for plasma membrane expression of both Ostalpha andOstbeta. These results demonstrate that the mouse Ostalpha-Ostbeta heteromerictransporter is a basolateral bile acid carrier and may be responsible for bileacid efflux in ileum and other ASBT-expressing tissues.