Functional role for stable microtubules in lens fiber cell elongation

Abstract

The process of tissue morphogenesis, especially for tissues reliant on the establishment of a specific cytoarchitecture for their functionality, depends a balanced interplay between cytoskeletal elements and their interactions with cell adhesion molecules. The microtubule cytoskeleton, which has many roles in the cell, is a determinant of directional cell migration, a process that underlies many aspects of development. We investigated the role of microtubules in development of the lens, a tissue where cell elongation underlies morphogenesis. Our studies with the microtubule depolymerizing agent nocodazole revealed an essential function for the acetylated population of stable microtubules in the elongation of lens fiber cells, which was linked to their regulation of the activation state of myosin. Suppressing myosin activation with the inhibitor blebbistatin could attenuate the loss of acetylated microtubules by nocodazole and rescue the effect of this microtubule depolymerization agent on both fiber cell elongation and lens integrity. Our results also suggest that acetylated microtubules impact lens morphogenesis through their interaction with N-cadherin junctions, with which they specifically associate in the region where lens fiber cell elongate. Disruption of the stable microtubule network increased N-cadherin junctional organization along lateral borders of differentiating lens fiber cells, which was prevented by suppression of myosin activity. These results reveal a role for the stable microtubule population in lens fiber cell elongation, acting in tandem with N-cadherin cell-cell junctions and the actomyosin network, giving insight into the cooperative role these systems play in tissue morphogenesis.

Deletion of Seventeen Amino Acids at the C-Terminal End of Aquaporin 0 Causes Distortion Aberration and Cataract in the Lenses of AQP0ΔC/ΔCMice

“…The C-terminal ends of intact AQP0 at the outer cortex interact with other proteins, such as beaded filament proteins filensin and CP49, to provide anchorage, fiber cell architecture, and lens biomechanics. Interaction of adhesion protein N-Cadherin and cytoskeletal elements during fiber cell elongation has been reported 69. CTCA is necessary to maintain the proper RING, which is low at the outer cortex and high in the central nucleus where it is more or less constant 70,71.…”

Early expression of Tubulin Beta-III in avian cranial neural crest cells

“…Microtubules function during cell division ( Memberg and Hall, 1995 ), migration ( Francis et al, 2011 ), and structural maintenance and changes ( Logan et al, 2018 ) among other cellular processes, and therefore, the expression of TUBB3 in NP cells during neurulation suggests that the beta-III isoform of the protein functions in one of these aspects at this stage. Since the NP is undergoing drastic morphological changes during neural tube closure, and the cells are also proliferating, the specific role of TUBB3 is difficult to pinpoint.…”

Microtubules: Evolving roles and critical cellular interactions

“…45,47,[59][60][61][62][63] Microtubules' role in cell functioning greatly depends on its ability to coordinate the functioning of other cellular elements, including other cytoskeletal components. [64][65][66][67][68] This has proven especially true in the field of cellular migration, with microtubules shown to have both direct and indirect effects on the actomyosin machinery in motile cells, partly through regulation of their stability. [64][65][66][67][68] Newer research has also demonstrated that microtubule interaction with cellular elements includes not only cytoskeletal elements and cytoplasmic organelles, but also cell-cell junctional proteins.…”

“…[64][65][66][67][68] This has proven especially true in the field of cellular migration, with microtubules shown to have both direct and indirect effects on the actomyosin machinery in motile cells, partly through regulation of their stability. [64][65][66][67][68] Newer research has also demonstrated that microtubule interaction with cellular elements includes not only cytoskeletal elements and cytoplasmic organelles, but also cell-cell junctional proteins. [68][69][70][71][72] Here, we look at the expanding role of microtubules in cellular functions and how microtubules may serve as a keystone of cytoskeletal coordination.…”

“…[64][65][66][67][68] Newer research has also demonstrated that microtubule interaction with cellular elements includes not only cytoskeletal elements and cytoplasmic organelles, but also cell-cell junctional proteins. [68][69][70][71][72] Here, we look at the expanding role of microtubules in cellular functions and how microtubules may serve as a keystone of cytoskeletal coordination.…”