Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain.
The cytoskeleton plays an important role in neuronal morphogenesis. We have identified and characterized a novel actin-binding protein, termed Mayven, predominantly expressed in brain. Mayven contains a BTB (broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure in the predicted N terminus and "kelch repeats" in the predicted C-terminal domain. Mayven shares 63% identity (77% similarity) with the Drosophila ring canal ("kelch") protein. Somatic cell-hybrid analysis indicated that the human Mayven gene is located on chromosome 4q21.2, whereas the murine homolog gene is located on chromosome 8. The BTB/POZ domain of Mayven can self-dimerize in vitro, which might be important for its interaction with other BTB/POZ-containing proteins. Confocal microscopic studies of endogenous Mayven protein revealed a highly dynamic localization pattern of the protein. In U373-MG astrocytoma/glioblastoma cells, Mayven colocalized with actin filaments in stress fibers and in patchy cortical actin-rich regions of the cell margins. In primary rat hippocampal neurons, Mayven is highly expressed in the cell body and in neurite processes. Binding assays and far Western blotting analysis demonstrated association of Mayven with actin. This association is mediated through the "kelch repeats" within the C terminus of Mayven. Depolarization of primary hippocampal neurons with KCl enhanced the association of Mayven with actin. This increased association resulted in dynamic changes in Mayven distribution from uniform to punctate localization along neuronal processes. These results suggest that Mayven functions as an actin-binding protein that may be translocated along axonal processes and might be involved in the dynamic organization of the actin cytoskeleton in brain cells.
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
M
M
Soltysik-Espanola
R A
RA
Rogers
S
S
Jiang
T A
TA
Kim
R
R
Gaedigk
R A
RA
White
H
H
Avraham
S
S
Avraham
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism; D019281:Dimerization; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D011189:Potassium Chloride / Q000494:pharmacology; D011233:Precipitin Tests; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; C485646:KLHL2 protein, human; C120754:Klhl2 protein, mouse; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride