p24 proteins and quality control of LIN-12 and GLP-1 trafficking in Caenorhabditis elegans.
Mutations in the Caenorhabditis elegans sel-9 gene elevate the activity of lin-12 and glp-1, which encode members of the LIN-12/NOTCH family of receptors. Sequence analysis indicates SEL-9 is one of several C. elegans p24 proteins. Allele-specific genetic interactions suggest that reducing sel-9 activity increases the activity of mutations altering the extracellular domains of LIN-12 or GLP-1. Reducing sel-9 activity restores the trafficking to the plasma membrane of a mutant GLP-1 protein that would otherwise accumulate within the cell. Our results suggest a role for SEL-9 and other p24 proteins in the negative regulation of transport of LIN-12 and GLP-1 to the cell surface, and favor a role for p24 proteins in a quality control mechanism for endoplasmic reticulum-Golgi transport.
Wen
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Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Greenwald
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D012734:Disorders of Sex Development; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D017238:Genes, Helminth / Q000235:genetics / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D006056:Golgi Apparatus / Q000737:chemistry / Q000378:metabolism; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology; D013489:Suppression, Genetic / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D015801:Helminth Proteins; C082460:Lin-12 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C119890:SEL-9 protein, C elegans