Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens

Hexagonal packing geometry is a hallmark of close-packed epithelial cells in metazoans. Here, we used fiber cells of the vertebrate eye lens as a model system to determine how the membrane skeleton controls hexagonal packing of post-mitotic cells. The membrane skeleton consists of spectrin tetramers...

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Bibliographic Details
Published in:The Journal of cell biology 2009-09, Vol.186 (6), p.915-928
Main Authors: Nowak, Roberta B, Fischer, Robert S, Zoltoski, Rebecca K, Kuszak, Jerome R, Fowler, Velia M
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - metabolism
Aging
Animals
Carrier Proteins - metabolism
Cell division
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell Shape
Cells
Epithelial Cells - metabolism
Epithelial Cells - ultrastructure
Lens, Crystalline - cytology
Lens, Crystalline - metabolism
Lens, Crystalline - ultrastructure
Maturation
Membranes
Mice
Mice, Knockout
Microfilament Proteins - metabolism
Morphology
Rodents
Tropomodulin - deficiency
Tropomodulin - genetics
Tropomodulin - metabolism
Tropomyosin - metabolism
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Summary:Hexagonal packing geometry is a hallmark of close-packed epithelial cells in metazoans. Here, we used fiber cells of the vertebrate eye lens as a model system to determine how the membrane skeleton controls hexagonal packing of post-mitotic cells. The membrane skeleton consists of spectrin tetramers linked to actin filaments (F-actin), which are capped by tropomodulin1 (Tmod1) and stabilized by tropomyosin (TM). In mouse lenses lacking Tmod1, initial fiber cell morphogenesis is normal, but fiber cell hexagonal shapes and packing geometry are not maintained as fiber cells mature. Absence of Tmod1 leads to decreased γTM levels, loss of F-actin from membranes, and disrupted distribution of β2-spectrin along fiber cell membranes. Regular interlocking membrane protrusions on fiber cells are replaced by irregularly spaced and misshapen protrusions. We conclude that Tmod1 and γTM regulation of F-actin stability on fiber cell membranes is critical for the long-range connectivity of the spectrin-actin network, which functions to maintain regular fiber cell hexagonal morphology and packing geometry.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200905065