Name: nuclear export signals and cargo
Uploaded: 2023-04-30T09:41:17.000Z
Duration: 1 min 42 s
Channel: JoVE

Nuclear export involves recognizing nuclear export signals or NES on the cargo protein.
NES are of three types: The classical 10-residue leucine-rich signal, a 38-residue M9 signal, and a 24-residue KNS signal.
NES are recognized by specialized nuclear transport receptors that shuttle the cargo through the nuclear pore complexes, or the NPC, on the nuclear membrane. Protein transport across the nucleus depends on the receptor binding to the small GTPase, Ran.
Protein exporting receptor&#8212; exportin 1 forms a complex with Ran-GTP and undergoes a conformational change. Exportin-Ran-GTP then binds the cargo to form a three-member complex.
The exportin-Ran-GTP-cargo complex shuttles through the NPC by interacting with the FG repeats on its inner lining and disrupts the gel-like selective barrier of the NPC to diffuse into the cytosol.
A GTPase activating protein called Ran-GAP present on the cytoplasmic fibrils of the NPC initiates hydrolysis of Ran-GTP to Ran-GDP. Ran-GDP induces a conformational change in exportin 1 that weakens its binding to the cargo and the complex disassembles.
After the receptors release the protein in the cytosol, exportin 1 and Ran-GDP move back to the nucleus f

nuclear export

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other non-canonical NES such as the M9 and KNS signal found in heteronuclear ribonucleoproteins or hnRNPs. Leucine-rich NES is present at the N-terminal end of a polypeptide and is characterized by stretches of leucine and isoleucine residues interspersed with small polar residues. The M9 signal sequence is 38-residues long and present in the C terminal domain of hnRNP A1. M9 signal sequence transports proteins and protein-bound mRNAs bidirectionally across the nucleus in a temperature-sensitive manner. M9 export signal can allow even nuclear-restricted proteins to move to the cytosol at high temperatures and restrict them inside the nucleus at low temperatures. The third non-canonical NES is the 24 amino acid-long KNS signal found in hnRNP K. Like M9, the KNS signal promotes bidirectional nuclear trafficking of proteins and RNA.
Specific nuclear exporters recognize each of these NES. For example, nuclear exporters such as chromosome region maintenance 1 (CRM1), also called exportin 1, recognize and export cargo with leucine-rich signal sequences. During cargo export, Ran-GTP binds to CRM1 to form the CRM1-RanGTP complex. This enables CRM1 and cargo interaction and the formation of a trimeric export complex. The cargo-exporter-RanGTP complex then interacts with the nucleoporins on the cytoplasmic fibrils of the nuclear pore complex or NPC to move across the nucleus. Nup358-RanBP complex on the NPC accelerates Ran GTP to GDP hydrolysis to disassemble the export complex and release the cargo in the cytosol. CRM1 and RanGDP are recycled back to the nucleus for multiple rounds of cargo export.

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring ...

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JoVE Core

Cell Biology

Unit 1

Intracellular Compartments and Protein Sorting

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KEY TERMS AND CONCEPTS

nuclear export signals and cargo

Nuclear export signals help proteins and RNA leave the nucleus and reach the right place in the cell. The nucleus also keeps some proteins inside by using a nuclear retention sequence, or NRS, which anchors them to the nuclear lamins and blocks movement to the cytosol.

Proteins that are not restricted can move after synthesis to the cytosol or to other organelles. They do this with the help of nuclear export signals, or NES. The transcript describes three NES types: the canonical leucine-rich signal and two non-canonical signals, M9 and KNS, found in heteronuclear ribonucleoproteins, or hnRNPs.

The leucine-rich NES is about 10 residues long and appears at the N-terminal end of a polypeptide. It contains stretches of leucine and isoleucine residues mixed with small polar residues. The M9 signal is 38 residues long and is found in the C-terminal domain of hnRNP A1. It can move proteins and protein-bound mRNAs in both directions across the nucleus in a temperature-sensitive way, and it can even let nuclear-restricted proteins move to the cytosol at high temperatures while keeping them in the nucleus at low temperatures.

The third non-canonical NES is the KNS signal. It is 24 amino acids long and is found in hnRNP K. Like M9, it supports bidirectional nuclear trafficking of proteins and RNA. Different nuclear exporters recognize these signals. For example, CRM1, also called exportin 1, exports cargo with leucine-rich signal sequences.

During export, Ran-GTP binds to CRM1 and forms a CRM1-RanGTP complex. This allows cargo to join the exporter and form a trimeric export complex. The complex then interacts with nucleoporins on the cytoplasmic fibrils of the nuclear pore complex, or NPC, and moves across the nucleus. On the NPC, the Nup358-RanBP complex speeds up Ran GTP hydrolysis to GDP, which breaks the export complex apart and releases the cargo in the cytosol. CRM1 and RanGDP then return to the nucleus for more rounds of cargo export.

Nuclear Export Signals and Cargo

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Nuclear export signals help proteins and RNA leave the nucleus and reach the right place in the cell. The nucleus also keeps some proteins inside by using a nuclear retention sequence, or NRS, which anchors them to the nuclear lamins and blocks movement to the cytosol. Proteins that are not restricted can move after synthesis to the cytosol or to other organelles. They do this with the help of nuclear export signals, or NES. The transcript describes three NES types: the canonical leucine-rich...

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key terms and concepts

Explore how nuclear export signals move proteins and RNA out of the nucleus, including leucine-rich NES, M9, KNS, CRM1, Ran-GTP, and the nuclear pore complex.

Nuclear Export Signals and Cargo | JoVE K12

cell biology

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Nuclear Export Signals and Cargo

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