Most human communication is nonverbal. When words fail our facial muscles take over, and an unguarded expression can be the most truthful message we send! But the most specialised of all facial muscles lie well out of sight. The extraocular muscles wrap around the back of the eyeball, giving the eye a high degree of mobility over the widest range of speeds. Margaret Briggs and Fred Schachat's fascination with the muscle began 15 years ago when a colleague told them about the heterogeneity of the muscle's contractile machinery. More recently, Briggs and Schachat have focused on the unique form of myosin found in the muscle, MYH13, which is responsible for the muscle's high-speed performance. Surprisingly, MYH13 only comprises 20-30% of the muscle's myosin component. How could a protein that comprises a relatively small fraction of the muscle determine its high-speed properties? Briggs and Schachat set about localising and quantifying the expression of MYH13 in one of the rabbit's six extraocular muscles, and discovered that MYH13 expression is restricted to a single region of the each muscle, spanning the innervation site of each fibre (p. 3133).
Myosin is the key protein in every muscle that drives contraction. Each fibre type in skeletal muscle has its own, specially adapted myosin isoform that defines the fibre's function. Briggs and Schachat were intrigued by the myosin in extraocular muscle, because it is also one of the oldest isoforms of the protein that has been found. But they were also puzzled by the ancient molecule's functional dominance at such low levels in the muscle. Briggs and Schachat reasoned that the MYH13 could be distributed through the muscle in one of two ways. Either a few specialised fibres in every muscle would be built entirely from MYH13, or the protein would be expressed in a large fraction of the muscle's fibres, but restricted to a few specialised regions.
Briggs began probing for the MYH13 protein throughout the length of an extraocular muscle by labelling the protein with an antibody that only recognised the specialised myosin. She also quantified the levels MYH13 in the muscle, using specialised protein-resolving gels. At first, Briggs didn't find any MYH13 protein in the regions of the muscle attached to the eyeball and skull, but as she moved towards the centre of the muscle, the antibody began picking up extraocular myosin molecules. The protein was tightly restricted to regions around each fibre's innervation site.
But how is the protein's expression controlled to produce this limited distribution? Briggs already knew that MYH13 protein is produced in response to activation signals sent from the nerve, but were the nerve's signals controlling the gene's transcription, or regulating protein expression? Briggs divided the muscle into three sections, and found that the MYH13 mRNA, like the protein, was localized to the central region of the muscle, which included the innervation zone. She explains that although the protein and its mRNA are found together, there is still a lot to be done before proving the mechanism that controls the ancient molecule's unique expression pattern.