Login processing...

Trial ends in Request Full Access Tell Your Colleague About Jove

16.7: Regulation of Nuclear Protein Sorting

JoVE Core
Cell Biology

A subscription to JoVE is required to view this content. Sign in or start your free trial.

Regulation of Nuclear Protein Sorting

16.7: Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the nucleus and, 5) secreting precursor proteins.

Masking of sorting signals

Nuclear transport is initiated as nuclear receptors bind to the nuclear localization signals (NLS) or nuclear export signals (NES). To limit the accessibility of the cargo to the nuclear receptors, NLS or NES can be masked by two types of mechanisms. In the first mechanism, the cargo protein undergoes conformational changes through disulfide bond formation or phosphorylation so that it no longer fits into the binding site of the receptor. In the second process, the cargo may bind another molecule, such as DNA, mRNA, or a protein, that interferes with its binding to the receptor.

Modifying nuclear receptors

Phosphorylation of importin alpha by casein kinase II upon binding to NLS of a cargo enhances its importin beta binding affinity and nuclear import. Alternatively, increased levels of importin beta can promote enhanced trafficking of its substrate by outcompeting other nuclear receptors for binding sites on the Nuclear Pore Complexes or NPCs.

Regulating Nuclear pore size

Nuclear pore size also controls the flux of protein transport. Cytoskeletal proteins help constrict or dilate the nuclear pore diameter to restrict cargo entering the nucleus. Alternatively, the extracellular matrix can stretch the nuclear envelope and expand the nuclear pores for cargo import.

Cargo retention

Nuclear trafficking is also restricted when cargo binds to cytosolic factors such as 14-3-3 protein or is tagged for degradation, inhibiting unnecessary transport across the nucleus.

Precursor secretion

Some proteins such as p105 are secreted in the cytoplasm as inactive precursors. Phosphorylation of p105 signals its cleavage to release an active P50 that can be transported to the nucleus.

Suggested Reading


Nuclear Protein Sorting Regulation Nucleus Composition Gene Expression Eukaryotic Cell Fate Nuclear Envelope Tightly Controlled Process Masking Cargo Signal Sequences Modifying Nuclear Receptor Affinity For Cargo Controlling Nuclear Pore Size Retaining Cargo During Transit Secreting Precursor Proteins Sorting Signals Masking Nuclear Transport Initiation Nuclear Localization Signals (NLS) Nuclear Export Signals (NES) Cargo Accessibility Limitation Conformational Changes Disulfide Bond Formation Phosphorylation Interference With Receptor Binding Modifying Nuclear Receptors Importin Alpha Phosphorylation By Casein Kinase II Importin Beta Binding Affinity Enhancement

Get cutting-edge science videos from JoVE sent straight to your inbox every month.

Waiting X
Simple Hit Counter