Functioning much like gears in a machine, cellular motor proteins are critical to dynamic functions throughout the body, including muscle contraction, cell migration and cellular growth processes. Now, neuroscientists from UC Irvine and the Florida campus of The Scripps Research Institute report that motor proteins also play a critical role in the stabilization of long-term memories. The findings add an unexpected dimension to the story of how memories are encoded and suggest new targets for therapeutic interventions.
UCI's Christopher Rex and Gavin Rumbaugh at Scripps found that myosin II proteins, more commonly studied in muscle contraction and cell migration, are critical for functional brain plasticity and learning. The work builds on a fundamental theory of memory – posed over 25 years ago by UCI neuroscientist Gary Lynch – that memories are the product of structural rearrangements of synapses in the brain.
"We suspected that motor proteins are involved in synaptic plasticity," said Rumbaugh, an assistant professor of neuroscience. "Now that we know that they are, we can begin to investigate how the vast literature on motor proteins from other cell types may generalize to neurons."
Study results appear in the Aug.26 issue of Neuron.
Myosin II motors are one of the most studied protein complexes in the human body. They are best known for interacting with actin filaments to control initiate forces within cellular compartments.
"Cells are constructed like buildings," said Rex, a Kauffman Foundation Fellow in anatomy & neurobiology. "Actin can be thought of as the building's frame, meaning it determines the scale and design of the structure. Myosin II would then be like a crane moving the beams into place. The main difference being that myosin II is poised to both tear down and rebuild the structure with a completely different design at any minute."
A core tenant of contemporary theory is that the sizes and shapes of dendritic spines, small protrusions at the receiving end of chemical transmission at synapses, are critical for determining synaptic strength.
"We know that appropriate patterns of neuronal activity can cause structural changes to these elements spines, now our major focus is to understand how this works," said Lynch, who contributed to the study.
Having discovered that a submicroscopic motor drives synaptic reorganization, the UCI and Scripps research groups believe they are substantially closer to understanding how to selectively enhance memory formation, and thereby treat the memory problems associated with aging, post-traumatic stress, mental retardation and age-related neurodegenerative diseases.
Christine Gall, Eniko Kramar, Lulu Chen and Yousheng Jia of UCI; Cristin Gavin and Courtney Miller of Scripps; Maria Rubio of the University of Alabama, Birmingham; Richard Huganir of Johns Hopkins University School of Medicine; and Nicholas Muzyczka of the University of Florida contributed to this work, which received support from the National Institutes of Health; the University of Alabama, Birmingham; the McKnight Brain Institute; Alabama Health Sciences Foundation; and the Kauffman Foundation.