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Post-translational events in the production of human lymphoblastoid interferon
Abstract:
Newly synthesized interferon and its mRNA were membrane-associated in a human lymphoblastoid cell (Namalwa) that had been induced with Sendai virus. Treatment with zinc, which acts as an inhibitor of proteolytic cleavage, prevented interferon production. When cytoskeletal function was disrupted by adding both colchicine and cytochalasin B to the induced Namalwa cells, secretion of interferon was inhibited. It is concluded that after translation of the interferon mRNA, the newly synthesized interferon polypeptide is discharged into the lumen of the endoplasmic reticulum, and undergoes a proteolytic cleavage before it is secreted by a process involving the cytoskeleton.
Insights
Newly synthesized interferon associates with cell membranes and requires proteolytic cleavage and cytoskeletal involvement for secretion. Zinc inhibits production, while colchicine and cytochalasin B disrupt the secretion process.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interferons are crucial signaling proteins in the innate immune system.
- The synthesis and secretion pathways of interferons are not fully elucidated.
- Human lymphoblastoid Namalwa cells are a model for studying viral induction responses.
Purpose of the Study:
- To investigate the cellular mechanisms involved in interferon synthesis and secretion.
- To determine the role of post-translational modification and cellular structures in interferon release.
Main Methods:
- Induction of human lymphoblastoid Namalwa cells with Sendai virus.
- Treatment with zinc to inhibit proteolytic cleavage.
- Disruption of cytoskeletal function using colchicine and cytochalasin B.
Main Results:
- Newly synthesized interferon and its mRNA were found to be membrane-associated.
- Zinc treatment inhibited interferon production, suggesting a role for proteolytic cleavage.
- Disruption of cytoskeletal function inhibited interferon secretion.
Conclusions:
- Interferon secretion involves its discharge into the endoplasmic reticulum lumen after translation.
- Proteolytic cleavage is a necessary step before interferon secretion.
- The cytoskeleton plays an active role in the secretion process of interferon.