Advancing Vesicle Trafficking Research

GenScript celebrates the accomplishments of the winners of the 2013 Nobel Prize in Physiology or Medicine. James Rothman, Randy Schekman, and Thomas Südhof shared the prize for their discoveries of the mechanisms of vesicle trafficking, a major transport system within cells that is crucial for the regulated secretion of neurotransmitters and other critical biomolecules.

Despite the advances recognized by this year's Nobel Prize, many open questions remain to be answered in the field of vesicle trafficking – and GenScript is committed to providing services that will accelerate future discoveries. Studies of the proteins that mediate vesicle trafficking, and of their variants that have been implicated in numerous diseases, can be aided by Gene Synthesis of Codon-Optimized sequences and Mutant Sequences or by Recombinant Protein Expression. For example:

Honigmann et al (Nature Structural & Molecular Biology 2013) ordered gene synthesis of mutant synaptotagmin-1 to probe the mechanisms of action of synaptotagmin-1, and discovered that it forms a bridge between phosphatidylserine in vesicle membranes and syntaxin-1 on the synaptic plasma membrane to promote vesicle recruitment and membrane fusion.

Wu et al. (J. Cell Biol. 2012) used 4 synthesized cDNAs encoding light chains of botulinum neurotoxin that specifically cleave different SNAP-25 protein members of the SNARE complex and thereby inhibit vesicle docking.

Serra et al. (PNAS 2010) ordered site-directed mutagenesis services to introduce the A454T mutation observed in a migraine patient population into the CACNA1A gene (encoding the P/Q Ca2+ channel α1 subunit), allowing them to uncover how P/Q channels are modulated by syntaxin 1A or SNAP-25 and showing that the A454T mutation decreased exocytosis.

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Image ©James Kegley

Randy Schekman started his research career working with yeast to identify over 50 genes that regulate vesicle formation, cargo-loading, processing by ER or Golgi, and transport to the cell membrane to enable secretion.

Image © Yale University

James Rothman used a biochemical approach in a cell-free system to identify and characterize the SNARE proteins that mediate the specificity of vesicle docking.

Image © Howard Hughes Medical Institute 2013 Photo: Tony Avela

Thomas Südhof focused on pre-synaptic neurons, which release neurotransmitters from vesicles in a manner that Sudhof showed depends upon calcium-sensing by synaptotagmin and many other synaptic proteins that mediate vesicle fusion.