Myosin-VI
Function in Sensory Hair Cells
of the Inner Ear
Myosin-VI is an unconventional
myosin with the remarkable property of motility towards the pointed
ends of actin filaments, the direction opposite to all other myosins
(Wells
et al 1999). Shown schematically in Fig
1, myosin-VI
is composed of an N-terminal motor domain, a light chain-binding
neck region, a 200 amino acid coiled-coil (CC) region and a highly
conserved C-terminal globular tail. Of these regions, the neck
domain is unusual in that it has a 50 amino acid linker between
the end of the motor and the single calmodulin binding 'IQ' motif.
It is this linker that likely is responsible for the unique motility
of myosin-VI (Wells
et al 1999).
Functionally, myosin-VI
is essential for the development of the inner ear in the mouse.
Myosin-VI mutations are responsible for deafness and balance defects
in the Snell's waltzer mouse (Avraham
et al 1995). Within the inner ear, a single cell type, the
sensory hair cell, expresses myosin-VI. In hair cells, myosin-VI
is located throughout the cell body but is highly enriched within
an actin-rich structure termed the cuticular plate (Fig.
2) (Avraham
et al 1995). The cuticular plate is found at the base of the
stereocilia, the actin-based protrusions that serve to sense and
transmit mechanoelectrical impulses. As such, the cuticular plate
serves to anchor the stereocilia into the apical cytoskeleton
of the sensory hair cell. The stereocilia are polarized, with
their pointed ends embedded in the cuticular plate, so myosin-VI
may also be required to transport components down the stereocilia.
Snell's waltzer mice have defects in the assembly of stereocilia
and it has been suggested that myosin-VI may be pulling the membranes
down between each stereocilium during hair cell development (Self
et al 1999).
Myosin-VI is also
concentrated within a region at the hair cell apex between the
cuticular plate and the junctional actin belt termed the 'pericuticular
necklace' (Hasson
et al 1997). This region of the hair cell is rich in membrane
vesicles, and therefore myosin-VI may be involved in shuttling
components into the cuticular plate or to the apical membrane.
There is no evidence that myosin-VI is itself able to associate
with membranes, so myosin-VI may instead be transported into the
pericuticular necklace by association with a cargo protein that
is membrane-bound. Recent work by Buss
et al (1998) has also suggested that myosin-VI is involved
in membrane trafficking, as they have observed myosin-VI enriched
within the trans-Golgi network in cultured cells.
Contributed by Tama
Hasson, UCSD
Recent Review
Miller, K.G. 1999. Myosin VI. In Guidebook to the Cytoskeletal
and Motor Proteins, Vol. 2. T. Kreis & R. Vale, eds. Oxford University
Press, NY. pp 445-447.
View cryoEM maps of myosin-VI
attached to F-actin.
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