Stabilization and remodeling of the membrane skeleton during lens fiber cell differentiation and maturation

Lee, Andria; Fischer, R.; Fowler, Velia M.

doi:10.1002/(sici)1097-0177(200003)217:3<257::aid-dvdy4>3.0.co;2-5

Cited by 86 publications

(47 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lens function is also critically dependent on intact intercellular-junctions (gap and adherens junctions), cell-extracellular matrix (ECM) interactions, and water channel function. [13][14][15][16][17][28][29][30] Given the extent of the morphological, cellular and biochemical deficits noted in the C3 lens, it is clearly evident that Rho GTPase functions as a critical determinant of normal lens growth, development and function. Rho GTPases regulate a wide range of biological processes including actin cytoskeleton organization, cell-cell adhesion, cell-ECM interactions, intracellular trafficking and transcriptional regulation through various signaling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Fiber cell differentiation is accompanied by cell elongation and remodeling of cytoskeletal structures. [13][14][15][16][17][18] Our knowledge of lens fiber cell elongation and cytoskeletal reorganization is limited, and the role of intracellular signaling pathways in these cellular processes remains to be elucidated. We have hypothesized that Rho GTPases (Rho and Rac) play a critical role in lens growth and function.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

Maddala

Pingping

Costello

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

To investigate the effects of Rho GTPase inactivation on lens fiber cell cytoskeletal and morphological integrity, a transgenic mouse model expressing C3-exoenzyme (a bacterial toxin) in a lens-specific manner was utilized. Cryosections of whole eyes from C3 transgenic mice and littermate controls were stained for F-actin with rhodamine-phalloidin or immunostained for b-catenin, aquaporin-0 or connexin-50, and confocal images were recorded. Lens fiber cell morphology was examined at both light and electron microscopic levels. To investigate the influence of Rho GTPase inactivation on the profiles of gene expression, cDNA libraries generated from transgenic and littermate control mouse lenses were screened by cDNA microarray analysis. In contrast to the wild-type lens, fiber cells of the transgenic lens were grossly swollen and disorganized, with abnormal membrane architecture. Staining of F-actin, b-catenin, aquaporin-0 and connexin-50 was reduced dramatically in the C3 transgenic lens as compared to controls. Western blot analysis and cDNA microarray analysis did not reveal any noticeable decreases in actin, b-catenin and aquaporin-0 protein levels or expression in C3 transgenic lenses, indicating that altered cytoskeletal organization in response to Rho GTPase inactivation might underlie the noted changes in staining for these proteins. Additionally, cDNA microarray analysis of C3 lens revealed altered expression (at least two-fold, compared to littermate controls) of 44 genes. These include genes encoding extracellular matrix and basement membrane proteins, cell survival and apoptotic pathways, and ion and protein transport. These data indicate that disruption of Rho GTPase function in the developing mouse lens results in abnormal cytoskeletal organization, fiber cell interactions, impaired lens fiber cell morphology and altered gene expression of cellular proteins involved in diverse functions. This work reveals that the morphological and cytoskeletal abnormalities triggered upon Rho GTPase inactivation in lens could be one of the important insults associated with cataract formation in C3 transgenic mouse lens.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

Maddala

Pingping

Costello

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…The preferential accumulation of the "early" GADs at the apical and basal tips of the lens fibers, which are the sites of active remodeling of the membrane skeleton during fiber elongation (Lee et al, 2000), indicates that GAD65 and EGAD and ultimately GABA may play a role in this process. Furthermore, the "early" GADs may be involved in cell signaling during formation of transient cell adhesion complexes between elongating fiber cells and overlying lens epithelium and/or the lens capsule at the posterior lens wall.…”

Section: Sequential Induction and Spatial Segregation Of Different Gamentioning

confidence: 99%

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Kwakowsky

Schwirtlich

Zhang

et al. 2007

Developmental Dynamics

View full text Add to dashboard Cite

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the adult nervous system and its biosynthetic enzyme glutamic acid decarboxylase (GAD) are abundantly expressed in the embryonic nervous system and are involved in the modulation of cell proliferation, migration, and differentiation. Here we describe for the first time the expression of GABA and embryonic and adult GAD isoforms in the developing mouse lens. We show that the GAD isoforms are sequentially induced with specific spatiotemporal profiles: GAD65 and embryonic GAD isoforms prevail in primary fibers, while GAD67 is the predominant GAD expressed in the postnatal secondary fibers. This pattern correlates well with the expression of Dlx2 and Dlx5, known as upstream regulators of GAD. GABA and GAD are most abundant at the tips of elongating fibers and are absent from organelle-free cells, suggesting their involvement is primarily in shaping of the cytoskeleton during fiber elongation stages. Developmental Dynamics 236: 3532-3544, 2007.

show abstract

“…Ultimately, the explanation for how a deficiency of ocrl1 leads to the Lowe syndrome phenotype must elucidate both why the target tissues are affected and why other tissues are not. The explanation may lie in the differential concentration of PIP 2 and PIP 3 in the apical or basolateral membranes of epithelial cells (Gassama-Diagne et al 2006;Pilot et al 2006), in the differential organization of the actin cytoskeleton in different cell types (Lee et al 2000;Yonemura et al 2004), or in the selective expression and trafficking of endocytic proteins in different tissues (Lutcke et al 1994). Further studies on the role of ocrl1 in various epithelial cell types may lead to a better understanding of the complex phenotype of Lowe syndrome.…”

Section: Increased Signalling In Lowe Cells Was Not Generalizedmentioning

confidence: 99%

“…PIP 2 plays an important role as a second messenger in regulating cell adhesion through the actin cytoskeleton (Raucher et al 2000). Since actin reorganization is required for the formation and maintenance of cellcell contacts (Lee et al 2000;Shen and Turner 2005), the defects in lens epithelial cell differentiation and renal proximal tubule function in Lowe syndrome could result, in part, from abnormalities in the actin cytoskeleton. We have previously shown that actin remodelling is disrupted in Lowe fibroblasts .…”

Section: Introductionmentioning

confidence: 99%

Abnormal bradykinin signalling in fibroblasts deficient in the PIP₂ 5‐phosphatase, ocrl1

Suchy

Cronin

Nussbaum

2009

J of Inher Metab Disea

View full text Add to dashboard Cite

Summary The oculocerebrorenal syndrome of Lowe (Lowe syndrome) is an X‐linked disorder of phosphatidylinositol metabolism characterized by congenital cataracts, renal proximal tubulopathy and neurological deficits. The disorder is due to the deficiency of the phosphatidylinositol 4,5‐bisphosphate (PIP2) 5‐phosphatase, ocrl1. PIP2 is critical for numerous cellular processes, including cell signalling, actin reorganization and protein trafficking, and is chronically elevated in patients with Lowe syndrome. The elevation of PIP2 cells of patients with Lowe syndrome provides the unique opportunity to investigate the roles of this phospholipid in fundamental cellular processes. We previously demonstrated that ocrl1 deficiency causes alterations in the actin cytoskeleton. Since actin remodelling is strongly activated by [Ca+2], which increases in response to IP3 production, we hypothesized that altered calcium signalling might contribute to the observed abnormalities in actin organization. Here we report a specific increase in bradykinin‐induced Ca+2 mobilization in Lowe fibroblasts. We show that the abnormal bradykinin signalling occurs in spite of normal total cellular receptor content. These data point to a novel role for ocrl1 in agonist‐induced calcium release.

show abstract

Stabilization and remodeling of the membrane skeleton during lens fiber cell differentiation and maturation

Cited by 86 publications

References 66 publications

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Abnormal bradykinin signalling in fibroblasts deficient in the PIP₂ 5‐phosphatase, ocrl1

Contact Info

Product

Resources

About

Stabilization and remodeling of the membrane skeleton during lens fiber cell differentiation and maturation

Cited by 86 publications

References 66 publications

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Abnormal bradykinin signalling in fibroblasts deficient in the PIP2 5‐phosphatase, ocrl1

Contact Info

Product

Resources

About

Abnormal bradykinin signalling in fibroblasts deficient in the PIP₂ 5‐phosphatase, ocrl1