Reference: Varlakhanova NV, et al. (2018) Feedback regulation of TORC1 by its downstream effectors Npr1 and Par32. Mol Biol Cell 29(22):2751-2765

Reference Help

Abstract


TORC1 (target of rapamycin complex) integrates complex nutrient signals to generate and fine-tune a growth and metabolic response. Npr1 (nitrogen permease reactivator) is a downstream effector kinase of TORC1 that regulates the stability, activity, and trafficking of various nutrient permeases including the ammonium permeases Mep1, Mep2, and Mep3 and the general amino acid permease Gap1. Npr1 exerts its regulatory effects on Mep1 and Mep3 via Par32 (phosphorylated after rapamycin). Activation of Npr1 leads to phosphorylation of Par32, resulting in changes in its subcellular localization and function. Here we demonstrate that Par32 is a positive regulator of TORC1 activity. Loss of Par32 renders cells unable to recover from exposure to rapamycin and reverses the resistance to rapamycin of Δ npr1 cells. The sensitivity to rapamycin of cells lacking Par32 is dependent on Mep1 and Mep3 and the presence of ammonium, linking ammonium metabolism to TORC1 activity. Par32 function requires its conserved repeated glycine-rich motifs to be intact but, surprisingly, does not require its localization to the plasma membrane. In all, this work elucidates a novel mechanism by which Npr1 and Par32 exert regulatory feedback on TORC1.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Varlakhanova NV, Tornabene BA, Ford MGJ
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference