We propose to extend the studies of cell junctions and cell membranes in the ocular lens of vertebrates. In order to maintain an avascular lens in a normal and transparent state, gap junctions are believed to play a crucial role in regulating ionic and metabolic communications between epithelial cells, between fiber cells, and between epithelial and fiber cells in the lens. Recent progress suggests that lens gap junctions consist of multiple connexins and structural types. The significance of the existence of multiple gap junction proteins and structures in the lens remains to be determined. We plan to investigate in greater detail the unique structural characteristics and functions of the controversial lens gap junctions. In addition, adherens junctions along with their cell adhesion molecules (cadherins) and actin bundles are thought to play an important role in governing lens development. We plan to study the differential expressions of cadherins during prenatal and postnatal lens development. Moreover, we will extend our research goals to gain some insights into the roles of cell membranes involved in receptor-mediated potocytosis. This newly-found mechanism may be involved in sequestering and transporting important small molecules necessary for normal lens growth. Finally, we will study the molecular motor, kinesin, and its association with microtubule-based organelle transport mechanisms required for the formation of a transparent lens. We will apply several new approaches and methodologies for these projects. These include scanning tunneling microscopy, rapid-freezing, freeze- substitution, deep freeze-etch electron microscopy, frozen-section immunofluorescence labeling, confocal laser scanning microscopy, immunocytochemistry using freeze-substitution preparations, thin-section electron microscopy using an improved fixative developed in our laboratory, tracer and cytochemical techniques, organ cultures, gel electrophoresis, and immunoblotting. The long-term objectives of this application are to gain a better understanding of the structure and functional role of cell junctions and cell membranes in the lens.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005314-16
Application #
2684495
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-09-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Cheng, Catherine; Nowak, Roberta B; Amadeo, Michael B et al. (2018) Tropomyosin 3.5 protects the F-actin networks required for tissue biomechanical properties. J Cell Sci 131:
Hu, Zhengping; Shi, Wen; Riquelme, Manuel A et al. (2017) Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation. Sci Rep 7:5298
Biswas, Sondip; Son, Alexander; Yu, Qili et al. (2016) Breakdown of interlocking domains may contribute to formation of membranous globules and lens opacity in ephrin-A5(-/-) mice. Exp Eye Res 145:130-139
Cheng, Catherine; Nowak, Roberta B; Biswas, Sondip K et al. (2016) Tropomodulin 1 Regulation of Actin Is Required for the Formation of Large Paddle Protrusions Between Mature Lens Fiber Cells. Invest Ophthalmol Vis Sci 57:4084-99
Cheng, Catherine; Nowak, Roberta B; Gao, Junyuan et al. (2015) Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells. Am J Physiol Cell Physiol 308:C835-47
Biswas, Sondip K; Brako, Lawrence; Gu, Sumin et al. (2014) Regional changes of AQP0-dependent square array junction and gap junction associated with cortical cataract formation in the Emory mutant mouse. Exp Eye Res 127:132-42
Biswas, Sondip K; Brako, Lawrence; Lo, Woo-Kuen (2014) Massive formation of square array junctions dramatically alters cell shape but does not cause lens opacity in the cav1-KO mice. Exp Eye Res 125:9-19
Lo, Woo-Kuen; Biswas, Sondip K; Brako, Lawrence et al. (2014) Aquaporin-0 targets interlocking domains to control the integrity and transparency of the eye lens. Invest Ophthalmol Vis Sci 55:1202-12
Zhang, Cheng; Asnaghi, Laura; Gongora, Celine et al. (2011) A developmental defect in astrocytes inhibits programmed regression of the hyaloid vasculature in the mammalian eye. Eur J Cell Biol 90:440-8
Biswas, Sondip K; Lee, Jai Eun; Brako, Lawrence et al. (2010) Gap junctions are selectively associated with interlocking ball-and-sockets but not protrusions in the lens. Mol Vis 16:2328-41

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