The Journal of Neuroscience, October 15, 2001, 21(20):7954-7968
Myr 8, A Novel Unconventional Myosin Expressed during Brain
Development Associates with the Protein Phosphatase Catalytic Subunits
1
and 1
1
Krishna G.
Patel,
Changdan
Liu,
Patricia L.
Cameron, and
Richard S.
Cameron
Section of Neurobiology, Institute of Molecular Medicine and
Genetics, Medical College of Georgia, Augusta, Georgia, 30912-3175
Directed neuronal, astroglial, and oligodendroglial cell migrations
comprise a prominent feature of mammalian brain development. Because
molecular motor proteins have been implicated in a wide spectrum of
processes associated with cell motility, we initiated studies to define
the pool of myosins in migrating cerebellar granule neurons and type-1
neocortical astrocytes. Our analyses identified two isoforms of a novel
unconventional myosin, which we have cloned, sequenced, and designated
myr 8a and 8b (eighth unconventional myosin from rat). Phylogenetic
analysis indicates that myr 8 myosins comprise a new class of myosins,
which we have designated class XVI. The head domain contains a large
N-terminal extension composed of multiple ankyrin repeats, which are
implicated in mediating an association with the protein phosphatase 1 (PP1) catalytic subunits 1
and 1
. The motor domain is followed by a single putative light-chain binding domain. The tail domain of myr 8a
is comparatively short with a net positive charge, whereas the tail
domain of myr 8b is extended, bears an overall neutral charge, and
reveals several stretches of poly-proline residues. Neither the myr 8a
nor the myr 8b sequence reveals
-helical coiled-coil motifs,
suggesting that these myosins exist as monomers. Both immunoblot and
Northern blot analyses indicate that myr 8b is the predominant isoform
expressed in brain, principally at developmental time periods. The
structural features and restricted expression patterns suggest that
members of this novel class of unconventional myosins comprise a
mechanism to target selectively the protein phosphatase 1 catalytic
subunits 1
and/or 1
in developing brain.
Key words:
unconventional myosins; cytoskeleton; nervous system; brain development; neuronal migration; astrocytes
Copyright © 2001 Society for Neuroscience 0270-6474/01/21207954-15$05.00/0