Genetically encoded intrabodies as high-precision tools to visualize and manipulate neuronal function

Abstract

Basic neuroscience research employs numerous forms of antibodies as key reagents in diverse applications. While the predominant use of antibodies is as immunolabeling reagents, neuroscientists are making increased use of intracellular antibodies or intrabodies. Intrabodies are recombinant antibodies genetically encoded for expression within neurons. These can be used to target various cargo (fluorescent proteins, reporters, enzymes, etc.) to specific molecules and subcellular domains to report on and manipulate neuronal function with high precision. Intrabodies have the advantages inherent in all genetically encoded recombinant antibodies but represent a distinct subclass in that their structure allows for their expression and function within cells. The high precision afforded by the ability to direct their expression to specific cell types, and the selective binding of intrabodies to targets within these allows intrabodies to offer unique advantages for neuroscience research, given the tremendous molecular, cellular and morphological complexity of brain neurons. Intrabodies expressed within neurons have been used for a variety of purposes in basic neuroscience research. Here I provide a general background to intrabodies and their development, and examples of their emerging utility as valuable basic neuroscience research tools.