The inefficient delivery of proteins, peptides, and peptide mimetics into the mammalian cell cytosol limits their potential as both research tools and potential therapeutics. This lecture will describe the discovery of a discrete “penta-arg” motif that traffics peptides and proteins into the cytosol by promoting efficient endosomal escape, a precise single-molecule tool that quantifies this trafficking event in live cells with accuracy and precision, and a genome screen that successfully identified the cellular machinery hijacked for this process. Our work provides new insight into how cells respond to unnatural endocytic cargo and how this knowledge can be exploited to improve the cytosolic delivery of proteins and peptide mimetics of diverse structure.

Purposefully moving peptides and proteins into the cytosol

253rd National Meeting (2017)

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