Myr 8, a novel unconventional myosin expressed during brain development associates with the protein phosphatase catalytic subunits 1alpha and 1gamma1.
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 1alpha and 1gamma. 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 alpha-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 1alpha and/or 1gamma in developing brain.
Patel
K G
KG
Section of Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia, 30912-3175, USA.
Liu
C
C
Cameron
P L
PL
Cameron
R S
RS
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D020134:Catalytic Domain / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009218:Myosins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D054645:Protein Phosphatase 1; D021122:Protein Subunits; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C438149:Myo16 protein, rat; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D021122:Protein Subunits; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D009218:Myosins