BIOMAT Database Logo BIOMAT Database Logo

Static retention of the lumenal monotopic membrane protein torsinA in the endoplasmic reticulum. 2011

Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, USA.

TorsinA is a membrane-associated enzyme in the endoplasmic reticulum (ER) lumen that is mutated in DYT1 dystonia. How it remains in the ER has been unclear. We report that a hydrophobic N-terminal domain (NTD) directs static retention of torsinA within the ER by excluding it from ER exit sites, as has been previously reported for short transmembrane domains (TMDs). We show that despite the NTD's physicochemical similarity to TMDs, it does not traverse the membrane, defining torsinA as a lumenal monotopic membrane protein and requiring a new paradigm to explain retention. ER retention and membrane association are perturbed by a subset of nonconservative mutations to the NTD, suggesting that a helical structure with defined orientation in the membrane is required. TorsinA preferentially enriches in ER sheets, as might be expected for a lumenal monotopic membrane protein. We propose that the principle of membrane-based protein sorting extends to monotopic membrane proteins, and identify other proteins including the monotopic lumenal enzyme cyclooxygenase 1 (prostaglandin H synthase 1) that share this mechanism of retention with torsinA.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009685 Nuclear Envelope The membrane system of the CELL NUCLEUS that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (NUCLEAR PORE). Nuclear Membrane,Envelope, Nuclear,Envelopes, Nuclear,Membrane, Nuclear,Membranes, Nuclear,Nuclear Envelopes,Nuclear Membranes
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004721 Endoplasmic Reticulum A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed) Ergastoplasm,Reticulum, Endoplasmic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D017384 Sequence Deletion Deletion of sequences of nucleic acids from the genetic material of an individual. Deletion Mutation,Deletion Mutations,Deletion, Sequence,Deletions, Sequence,Mutation, Deletion,Mutations, Deletion,Sequence Deletions

Related Publications

Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
TorsinA participates in endoplasmic reticulum-associated degradation.
July 2011, Nature communications,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
TorsinA and the torsinA-interacting protein printor have no impact on endoplasmic reticulum stress or protein trafficking in yeast.
January 2011, PloS one,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
C-terminal, endoplasmic reticulum-lumenal domain of prosurfactant protein C - structural features and membrane interactions.
February 2008, The FEBS journal,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Retention of membrane proteins by the endoplasmic reticulum.
November 1985, The Journal of cell biology,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Lumenal proteins of the mammalian endoplasmic reticulum are required to complete protein translocation.
June 1993, Cell,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.
September 1997, Molecular biology of the cell,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endoplasmic reticulum.
August 2015, Journal of cell science,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Membrane protein insertion at the endoplasmic reticulum.
January 2011, Annual review of cell and developmental biology,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Protein transport across the endoplasmic reticulum membrane.
September 2008, The FEBS journal,
Abigail B Vander Heyden, and Teresa V Naismith, and Erik L Snapp, and Phyllis I Hanson
Membrane protein integration into the endoplasmic reticulum.
October 2011, The FEBS journal,
Copied contents to your clipboard!