The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
A signal peptide is a short peptide present at the N-terminus of most newly synthesized proteins that are destined toward the secretory pathway. These proteins include those that reside either inside certain organelles, secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, most type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide.
The translocon is a complex of proteins associated with the translocation of polypeptides across membranes. In eukaryotes the term translocon most commonly refers to the complex that transports nascent polypeptides with a targeting signal sequence into the interior space of the endoplasmic reticulum (ER) from the cytosol. This translocation process requires the protein to cross a hydrophobic lipid bilayer. The same complex is also used to integrate nascent proteins into the membrane itself. In prokaryotes, a similar protein complex transports polypeptides across the (inner) plasma membrane or integrates membrane proteins. In either case, the protein complex is formed from Sec proteins, with the hetero-trimeric Sec61 being the channel. In prokaryotes, the homologous channel complex is known as SecYEG.
Sec61, termed SecYEG in prokaryotes, is a membrane protein complex found in all domains of life. As the core component of the translocon, it transports proteins to the endoplasmic reticulum in eukaryotes and out of the cell in prokaryotes. It is a doughnut-shaped pore through the membrane with 3 different subunits (heterotrimeric), SecY (α), SecE (γ), and SecG (β). It has a region called the plug that blocks transport into or out of the ER. This plug is displaced when the hydrophobic region of a nascent polypeptide interacts with another region of Sec61 called the seam, allowing translocation of the polypeptide into the ER lumen.
Peter Walter is a German-American molecular biologist and biochemist. He is currently the Director of the Bay Area Institute of Science at Altos Labs and an emeritus professor at the Department of Biochemistry and Biophysics of the University of California, San Francisco (UCSF). He was a Howard Hughes Medical Institute (HHMI) Investigator until 2022.
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.
Protein transport protein Sec61 subunit beta is a protein that in humans is encoded by the SEC61B gene.
Translocon-associated protein subunit alpha is a protein that in humans is encoded by the SSR1 gene.
Derlin-1 also known as degradation in endoplasmic reticulum protein 1 is a membrane protein that in humans is encoded by the DERL1 gene. Derlin-1 is located in the membrane of the endoplasmic reticulum (ER) and is involved in retrotranslocation of specific misfolded proteins and in ER stress. Derlin-1 is widely expressed in thyroid, fat, bone marrow and many other tissues. The protein belongs to the Derlin-family proteins consisting of derlin-1, derlin-2 and derlin-3 that are components in the endoplasmic reticulum-associated protein degradation (ERAD) pathway. The derlins mediate degradation of misfolded lumenal proteins within ER, and are named ‘der’ for their ‘Degradation in the ER’. Derlin-1 is a mammalian homologue of the yeast DER1 protein, a protein involved in the yeast ERAD pathway. Moreover, derlin-1 is a member of the rhomboid-like clan of polytopic membrane proteins.
Translocon-associated protein subunit beta also known as TRAP-beta is a protein that in humans is encoded by the SSR2 gene.
Protein transport protein Sec61 subunit gamma is a protein that in humans is encoded by the SEC61G gene.
Martin J. Lohse is a German physician and pharmacologist.
A target peptide is a short peptide chain that directs the transport of a protein to a specific region in the cell, including the nucleus, mitochondria, endoplasmic reticulum (ER), chloroplast, apoplast, peroxisome and plasma membrane. Some target peptides are cleaved from the protein by signal peptidases after the proteins are transported.
The Schleiden Medal is an award given by the Academy of Sciences Leopoldina, the National Academy of Germany, to honour outstanding achievements in the field of cellular biology. The award is named after botanist Matthias Jakob Schleiden.
Ramanujan Shankar Hegde is a group leader at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).
Dieter Oesterhelt was a German biochemist. From 1980 until 2008, he was director of the Max Planck Institute for Biochemistry, Martinsried.
Wolfgang P. Baumeister is a German molecular biologist and biophysicist. His research has been pivotal in the development of Cryoelectron tomography.
Dirk Görlich, born October 18, 1966, in Halle (Saale) of Germany, is a German biochemist. He is now director at the Max Planck Institute for Multidisciplinary Sciences in Göttingen.
Gia Voeltz is an American cell biologist. She is a professor of Molecular, Cellular and Developmental Biology at the University of Colorado Boulder and a Howard Hughes Medical Institute Investigator. She is known for her research identifying the factors and unraveling the mechanisms that determine the structure and dynamics of the largest organelle in the cell: the endoplasmic reticulum. Her lab has produced paradigm shifting studies on organelle membrane contact sites that have revealed that most cytoplasmic organelles are not isolated entities but are instead physically tethered to an interconnected ER membrane network.
