Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 16, Issue 5, Pages 2443-2457Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E04-12-1116
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Funding
- NIDDK NIH HHS [R01 DK025387, P01 DK055389, DK-25387, F32 DK010113, R56 DK025387, T32 DK007017, R37 DK025387, DK-07017, DK-55389, DK-10113] Funding Source: Medline
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To develop our understanding of myosin-1a function in vivo, we have created a mouse line null for the myosin-la gene. Myosin-1a knockout mice demonstrate no overt phenotypes at the whole animal level but exhibit significant perturbations and signs of stress at the cellular level. Among these are defects in microvillar membrane morphology, distinct changes in brush-border organization, loss of numerous cytoskeletal and membrane components from the brush border, and redistribution of intermediate filament proteins into the brush border. We also observed significant ectopic recruitment of another short-tailed class I motor, myosin-1c, into the brush border of knockout enterocytes. This latter finding, a clear demonstration of functional redundancy among vertebrate myosins-I, may account for the lack of a whole animal phenotype. Nevertheless, these results indicate that myosin-1a is a critical multifunctional component of the enterocyte, required for maintaining the normal composition and highly ordered structure of the brush border.
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