1. Is synaptotagmin the calcium sensor?
Motojiro Yoshihara, Bill Adolfsen, J Troy Littleton Curr Opin Neurobiol. 2003 Jun;13(3):315-23. doi: 10.1016/s0959-4388(03)00063-1.
After much debate, recent progress indicates that the synaptic vesicle protein synaptotagmin I probably functions as the calcium sensor for synchronous neurotransmitter release. Following calcium influx into presynaptic terminals, synaptotagmin I rapidly triggers the fusion of synaptic vesicles with the plasma membrane and underlies the fourth-order calcium cooperativity of release. Biochemical and genetic studies suggest that lipid and SNARE interactions underlie synaptotagmin's ability to mediate the incredible speed of vesicle fusion that is the hallmark of fast synaptic transmission.
2. Production and Evaluation of the Properties of HIV-1-Nef-MPER-V3 Fusion Protein Harboring IMT-P8 Cell Penetrating Peptide
Shekoufa Jahedian, Seyed Mehdi Sadat, Gholam Reza Javadi, Azam Bolhassani Curr HIV Res. 2020;18(5):315-323. doi: 10.2174/1570162X18666200612151925.
Background: Finding a safe and effective vaccine for HIV-1 infection is still a major concern. Objective: This study aimed to design and produce a recombinant Nef-MPER V3 protein fused with IMT-P8 using E. coli expression system to provide a potential HIV vaccine with high cellular penetrance. Methods: After synthesizing the DNA sequence of the fusion protein, the construct was inserted into the pET-28 expression vector. The recombinant protein expression was induced using 1 mM IPTG and the product was purified through affinity chromatography. Characterization of cellular delivery, toxicity and immunogenicity of the protein was carried out. Results: The recombinant protein was expressed and confirmed by the anti-Nef antibody through western blotting. Data analyses showed that the protein possessed no considerable toxicity effect and has improved the IMT-P8 penetration rate in comparison to a control sample. Moreover, the antigen immunogenicity of the protein induced specific humoral response in mice. Conclusion: It was concluded that IMT-P8-Nef-MPER-V3 fusion protein has a high penetrance rate in mammalian cell line and low toxicity, thus it can be potentially considered as a vaccine against HIV-1.
3. Cytokines in rheumatoid arthritis: trials and tribulations
N L Carteron Mol Med Today. 2000 Aug;6(8):315-23. doi: 10.1016/s1357-4310(00)01757-3.
Biological agents that inhibit the activity of proinflammatory cytokines are being investigated for use in the treatment of rheumatoid arthritis. Thus far, two of these agents, both of which neutralize tumor necrosis factor alpha (TNF-alpha), have received US Food and Drug Administration approval for the treatment of the disease. Etanercept is a bioengineered fusion protein of the p75 soluble TNF receptor, and infliximab is a chimeric monoclonal antibody to TNF-alpha. Other agents that target proinflammatory cytokines are also being developed. By allowing earlier treatment and better-tolerated long-term therapy, biologics might help slow or prevent disease progression and joint destruction.
