Ribosome-associated vesicle

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Ribosome-associated vesicles, also known as RAVs, are novel sub-compartments of the rough endoplasmic reticulum (ER), a membranous cellular network that is important for the synthesis and transport of proteins. RAVs have been observed via multiple imaging techniques and appear as discrete spherical vesicles that are associated with actively translated ribosomes. [1] It is hypothesized that RAVs may arise from structural and/or functional changes in local membrane curvature along the rough endoplasmic reticulum's tubular membrane network.

Contents

Discovery

RAVs were first identified in the pancreatic β-cell-derived INS1-E cells of rats, using a combination of live-cell super-resolution stimulated-emission-depletion microscopy (STED) and highly-inclined thin illumination (HiLO), with high-speed, three-dimensional (3D) wide-field imaging. This approach was integrated with in situ cryo-electron tomography (Cryo-ET) and cryo-correlative light and electron microscopy (Cryo-CLEM) to visualize ER network dynamics, including relationships with other intracellular organelles, including mitochondria. [1]

Characteristics

Classically, ER tubules tend to be highly curved and free of ribosomes, whereas ER sheets lack curvature but have ribosomes. [2] In contrast, RAVs are formed from highly curved structures with ribosomes. RAVs are also known to be dynamic, moving throughout the cell over distances as long as 5 μm. These vesicular structures are primarily found in the cell periphery near microtubule tracks and the ER reticular network. Furthermore, RAVs and ER interact closely via direct contacts.

RAVs have been characterized in multiple cell types across different organs. This includes primary human fibroblasts, mouse embryonic fibroblasts, and human BE(2)-M17 cells, a dopamine-secreting, neuron-derived cell line. Carter, et al., were able to apply their findings to primary rat cortical neurons, as well. Similar to pancreatic cells, neuronal RAVs are also highly dynamic and show movement along the length of dendrites. Live imaging studies show RAVs in both neurons and INS1-1E cells stalling at times, [1] consistent with other dynamic intracellular structures that stall upon recruitment to sites of local translation. [3]

Proposed Function

It is hypothesized that RAVs may represent a novel mechanism by which secretory cells can answer to the demanding workload of protein synthesis, due to the dynamic nature of RAVs. The hybrid morphology of the RAVs is thought to serve as a way for the secretory cells to harness the protein production of the rough ER combined with the mobility of the tubular smooth ER. [4]

Studies have suggested that local translation may play a critical role in activity-dependent synaptic plasticity and neuron remodelling. [5] [6] While thousands of mRNAs are trafficked to dendrites for site-specific translation, the machinery for this translation has yet to be fully elucidated. Carter, et al., propose that RAVs may facilitate site-specific local translation in neurons by coupling cell activity and protein synthesis, [1] consistent with other dynamic intracellular structures that stall upon recruitment to sites of local translation. [3]

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

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.

<span class="mw-page-title-main">Endomembrane system</span> Membranes in the cytoplasm of a eukaryotic cell

The endomembrane system is composed of the different membranes (endomembranes) that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, vesicles, endosomes, and plasma (cell) membrane among others. The system is defined more accurately as the set of membranes that forms a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport. Importantly, the endomembrane system does not include the membranes of plastids or mitochondria, but might have evolved partially from the actions of the latter.

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.

<span class="mw-page-title-main">Vesicle (biology and chemistry)</span> Any small, fluid-filled, spherical organelle enclosed by a membrane

In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, the vesicles are called unilamellar liposomes; otherwise they are called multilamellar liposomes. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.

The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes.

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 are formed from Sec proteins, with the heterotrimeric Sec61 being the channel. In prokaryotes, the homologous channel complex is known as SecYEG.

In cell biology, microsomes are heterogeneous vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.

<span class="mw-page-title-main">Soma (biology)</span> Portion of a brain cell containing its nucleus

In cellular neuroscience, the soma, perikaryon, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes vary from as small as about 5 micrometres to over 10 millimetres for some of the smallest and largest neurons of invertebrates, respectively.

<span class="mw-page-title-main">Endoplasm</span> Also known as entoplasm

Endoplasm generally refers to the inner, dense part of a cell's cytoplasm. This is opposed to the ectoplasm which is the outer (non-granulated) layer of the cytoplasm, which is typically watery and immediately adjacent to the plasma membrane. The nucleus is separated from the endoplasm by the nuclear envelope. The different makeups/viscosities of the endoplasm and ectoplasm contribute to the amoeba's locomotion through the formation of a pseudopod. However, other types of cells have cytoplasm divided into endo- and ectoplasm. The endoplasm, along with its granules, contains water, nucleic acids, amino acids, carbohydrates, inorganic ions, lipids, enzymes, and other molecular compounds. It is the site of most cellular processes as it houses the organelles that make up the endomembrane system, as well as those that stand alone. The endoplasm is necessary for most metabolic activities, including cell division.

A secretory protein is any protein, whether it be endocrine or exocrine, which is secreted by a cell. Secretory proteins include many hormones, enzymes, toxins, and antimicrobial peptides. Secretory proteins are synthesized in the endoplasmic reticulum.

<span class="mw-page-title-main">Cellular compartment</span> Closed part in cytosol

Cellular compartments in cell biology comprise all of the closed parts within the cytosol of a eukaryotic cell, usually surrounded by a single or double lipid layer membrane. These compartments are often, but not always, defined as membrane-bound organelles. The formation of cellular compartments is called compartmentalization.

<span class="mw-page-title-main">Nissl body</span> Rough endoplasmic reticulum structure found in neurons

In cellular neuroscience, Nissl bodies are discrete granular structures in neurons that consist of rough endoplasmic reticulum, a collection of parallel, membrane-bound cisternae studded with ribosomes on the cytosolic surface of the membranes. Nissl bodies were named after Franz Nissl, a German neuropathologist who invented the staining method bearing his name. The term "Nissl bodies" generally refers to discrete clumps of rough endoplasmic reticulum and free ribosomes in nerve cells. Masses of rough endoplasmic reticulum also occur in some non-neuronal cells, where they are referred to as ergastoplasm, basophilic bodies, or chromophilic substance. While these organelles differ in some ways from Nissl bodies in neurons, large amounts of rough endoplasmic reticulum are generally linked to the copious production of proteins.

The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It has been found to be conserved between mammalian species, as well as yeast and worm organisms.

<span class="mw-page-title-main">KDELR1</span> Protein-coding gene in the species Homo sapiens

KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1, also known as KDELR1, is a protein which in humans is encoded by the KDELR1 gene.

In cell biology, membrane bound polyribosomes are attached to a cell's endoplasmic reticulum. When certain proteins are synthesized by a ribosome they can become "membrane-bound". The newly produced polypeptide chains are inserted directly into the endoplasmic reticulum by the ribosome and are then transported to their destinations. Bound ribosomes usually produce proteins that are used within the cell membrane or are expelled from the cell via exocytosis.

Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small as 10 nm or wider, with no clear upper limit. These zones of apposition are highly conserved in evolution. These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids and reactive oxygen species. MCS are important in the function of the endoplasmic reticulum (ER), since this is the major site of lipid synthesis within cells. The ER makes close contact with many organelles, including mitochondria, Golgi, endosomes, lysosomes, peroxisomes, chloroplasts and the plasma membrane. Both mitochondria and sorting endosomes undergo major rearrangements leading to fission where they contact the ER. Sites of close apposition can also form between most of these organelles most pairwise combinations. First mentions of these contact sites can be found in papers published in the late 1950s mainly visualized using electron microscopy (EM) techniques. Copeland and Dalton described them as “highly specialized tubular form of endoplasmic reticulum in association with the mitochondria and apparently in turn, with the vascular border of the cell”.

Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies.

<span class="mw-page-title-main">Cranio-lenticulo-sutural dysplasia</span> Medical condition

Cranio-lenticulo-sutural dysplasia is a neonatal/infancy disease caused by a disorder in the 14th chromosome. It is an autosomal recessive disorder, meaning that both recessive genes must be inherited from each parent in order for the disease to manifest itself. The disease causes a significant dilation of the endoplasmic reticulum in fibroblasts of the host with CLSD. Due to the distension of the endoplasmic reticulum, export of proteins from the cell is disrupted.

<span class="mw-page-title-main">Intracellular transport</span> Directed movement of vesicles and substances within a cell

Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Since intracellular transport heavily relies on microtubules for movement, the components of the cytoskeleton play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles, mRNA, and chromosomes.

References

  1. 1 2 3 4 Carter, Stephen D.; Hampton, Cheri M.; Langlois, Robert; Melero, Roberto; Farino, Zachary J.; et al. (April 3, 2020). "Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells". Science Advances. 6 (14): eaay9572. Bibcode:2020SciA....6.9572C. doi:10.1126/sciadv.aay9572. PMC   7112762 . PMID   32270040.
  2. ↑ Schwarz, D. S.; Blower, M. D. (2015). "The endoplasmic reticulum: structure, function and response to cellular signaling - PMC". Cellular and Molecular Life Sciences. 73 (1): 79–94. doi:10.1007/s00018-015-2052-6. PMC   4700099 . PMID   26433683.
  3. 1 2 Spillane, Mirela; Ketschek, Andrea; Merianda, Tanuja T.; Twiss, Jeffery L.; Gallo, Gianluca (December 26, 2013). "Mitochondria Coordinate Sites of Axon Branching through Localized Intra-axonal Protein Synthesis". Cell Reports. 5 (6): 1564–1575. doi:10.1016/j.celrep.2013.11.022. PMC   3947524 . PMID   24332852.
  4. ↑ Farrell, Ryan J.; Ryan, Timothy A. (September 1, 2020). "Local Sourcing of Secretory Proteins in Faraway Places". Trends in Neurosciences. 43 (9): 649–650. doi:10.1016/j.tins.2020.06.004. PMID   32546404. S2CID   219726585 – via www.cell.com.
  5. ↑ Baj, Gabriele; Pinhero, Vera; Vaghi, Valentina; Tongiorgi, Enrico (July 15, 2016). "Signaling pathways controlling activity-dependent local translation of BDNF and their localization in dendritic arbors". Journal of Cell Science. 129 (14): 2852–2864. doi:10.1242/jcs.177626. hdl: 11368/2922417 . PMID   27270670. S2CID   10266514 – via PubMed.
  6. ↑ Fernandez-Moya, Sandra M.; Bauer, Karl E.; Kiebler, Michael A. (April 8, 2014). "Meet the players: local translation at the synapse". Frontiers in Molecular Neuroscience. 7: 84. doi: 10.3389/fnmol.2014.00084 . PMC   4227489 . PMID   25426019.
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