Coincident loss of mitochondria and nuclei during lens fiber cell differentiation

Bassnett, Steven; Beebe, David C.

doi:10.1002/aja.1001940202

Cited by 200 publications

(166 citation statements)

References 18 publications

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“…For example, as part of their differentiation program, lens ®ber cells undergo a precisely timed, massive destruction of all intracellular organelles, including the nucleus (Bassnett and Beebe, 1992;Vrensen et al, 1991;Kuwabara and Imaizumi, 1974). This process is associated with expression of Cdc2 (Gao et al, 1995;He et al, 1997, observations), the enzyme responsible for nuclear envelope breakdown during mitosis (Gallant and Nigg, 1992).…”

Section: Discussionmentioning

confidence: 99%

pRb and p107 regulate E2F activity during lens fiber cell differentiation

et al. 1998

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During growth arrest and di erentiation, activity of the E2F family of transcription factors is inhibited by interactions with pRb and the related proteins, p107 and p130. To determine which members of the E2F and pRb families may contribute to growth arrest as lens epithelial cells di erentiate into ®ber cells, we examined the expression of individual E2F species and characterized the E2F protein complexes formed in rat lens epithelia and ®bers. RT/PCR detected all ®ve known members of the E2F family in lens epithelial cells, but only E2F-1, E2F-3, and E2F-5 in ®ber cells. Proteins extracted from lens epithelia of newborn rats formed at least two speci®c complexes with an E2F consensus oligonucleotide. Proteins from lens ®ber cells formed three speci®c complexes, one of which comigrated with an epithelial cell complex. Incubation of epithelial and ®ber cell extracts with an antibody speci®c for p107 demonstrated that two ®ber cell complexes and one epithelial cell complex contained p107. Although the remaining ®ber cell complex did not react with antibodies to pRb or p130 in this assay, a strong reaction with pRb antibody was observed when the electromobility shifted complexes were subsequently immunoblotted (shift/Western assay). Immunocytochemistry con®rmed that pRb protein is present in the nuclei of both epithelial cells and ®ber cells. Immunoblotting of whole cell extracts with pRb antibody showed multiple, phosphorylated forms of pRb in the epithelial cells, but predominantly hypophosphorylated pRb in the ®ber cells. None of the complexes formed with E2F were recognized exclusively by the p130 antibody, although the previously identi®ed p107 complexes reacted weakly. The absence of p130/E2F complexes was correlated with the presence of multiple ubiquitinated forms of p130, especially in the ®ber cells. Thus, although p130/E2F complexes are implicated in the terminal di erentiation of many cell types, in di erentiating lens ®ber cells pRb and p107 seem to be the primary regulators of E2F activity.

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Section: Discussionmentioning

confidence: 99%

pRb and p107 regulate E2F activity during lens fiber cell differentiation

et al. 1998

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“…1A). Of particular interest were the day 6 embryo, when the lens first appears transparent (27), the day 8 -10 embryo, when organelle breakdown begins (28), and the day 12 embryo, when an organelle-free zone is first observed. When non-crystallin proteins were loaded equivalently (Fig.…”

Section: Spectrin Is Cleaved To Discrete Fragments During Lensmentioning

confidence: 99%

Caspase Remodeling of the Spectrin Membrane Skeleton during Lens Development and Aging

Lee

Morrow

Fowler

2001

Journal of Biological Chemistry

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Terminal differentiation of lens fiber cells resembles the apoptotic process in that organelles are lost, DNA is fragmented, and changes in membrane morphology occur. However, unlike classically apoptotic cells, which are disintegrated by membrane blebbing and vesiculation, aging lens fiber cells are compressed into the center of the lens, where they undergo cell-cell fusion and the formation of specialized membrane interdigitations. In classically apoptotic cells, caspase cleavage of the cytoskeletal protein ␣-spectrin to ϳ150-kDa fragments is believed to be important for membrane blebbing. We report that caspase(s) cleave ␣-spectrin to ϳ150-kDa fragments and ␤-spectrin to ϳ120-and ϳ80-kDa fragments during late embryonic chick lens development. These fragments continue to accumulate with age so that in the oldest fiber cells of the adult lens, most, if not all, of the spectrin is cleaved to discrete fragments. Thus, unlike classical apoptosis, where caspase-cleaved spectrin is short lived, lens fiber cells contain spectrin fragments that appear to be stable for the lifetime of the organism. Moreover, fragmentation of spectrin results in reduced membrane association and thus may lead to permanent remodeling of the membrane skeleton. Partial and specific proteolysis of membrane skeleton components by caspases may be important for age-related membrane changes in the lens.The spectrin-actin membrane skeleton underlies the plasma membranes of all cells and is important for cellular shape, membrane stability and deformability, as well as the formation of membrane subdomains (1). The major component of the membrane skeleton, spectrin, is composed of an ␣/␤ heterodimer that self-associates head-to-head to form a 200-nm extended tetramer filament. Spectrin cross-links actin filaments into an isotropic meshwork. This spectrin-actin meshwork is attached to the membrane by direct interactions of ␤-spectrin with membrane proteins and indirect interactions of ␤-spectrin with membrane attachment proteins such as ankyrin (2).Proteolysis of ␣-spectrin (␣II-spectrin, non-erythroid spectrin, or fodrin) to discrete fragments is implicated in changes in cell shape and membrane morphology which occur in many cell types. During platelet activation, which includes a cell shape transformation from discs into irregular spheres, spectrin is cleaved to ϳ150-kDa fragments by the calcium-dependent protease, calpain (3). ␣-Spectrin cleavage by calpain has also been implicated in cellular hypoxia (4), neuronal injury and degeneration (5), and neuronal growth cone formation (6). However, in apoptotic cells, ␣-spectrin proteolysis to ϳ150-kDa fragments is mediated by caspases; in these cells, spectrin proteolysis is thought to be important for the disintegration of the plasma membranes via formation of vesicular "apoptotic bodies" (7-12). Although calpain cleavage of spectrin is known to affect its ability to bind membranes or actin filaments (13, 14), the detailed consequences of caspase cleavage of spectrin have not been studied.The terminal ...

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“…A number of studies have shown that all organelles including nuclei and mitochondria of lens fibers degenerate (Bassnett and Beebe, 1992), but that the morphology of degeneration depends on the origin of the fiber cell. In the mouse, organelles of primary fiber cells undergo degeneration a few days after they have reached the lens epithelium at their anterior tip at about embryonic day 16 (Vrensen et al, 1991).…”

Section: Is Fiber Cell Denucleation Related To Apoptosis?mentioning

confidence: 99%

Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege

Lang

1997

Cell Death Differ

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Formation of the mammalian eye requires a complex series of tissue interactions that result in an organ of exquisite sensory capability. The early steps in eye development involve extensive cell death associated with morphogenesis. Later, suppression of programmed cell death is essential for tissue differentiation and in the adult, the immune privileged status of the eye is maintained in part through factors that induce inflammatory cell apoptosis. Experimental evidence suggests that suppression of apoptosis in cells of the lens lineage by fibroblast growth factors is one component of their action during lens morphogenesis. Fibroblast growth factors are also required for normal lens fiber-cell differentiation. This includes a degenerative step for organelles that is presumably an adaptation for the clearance of light scattering elements from the optic axis. The process of organelle degeneration may be related to apoptosis in a few of its features. Activelyinduced apoptosis becomes important for eye development as the temporary ocular vasculatures regress. This too, is presumably an adaptation for the disposal of cells that would disturb the passage of light to the retina. Ocular macrophages appear to be essential for the induction of apoptosis in the endothelial cells comprising the ocular vasculatures. In the adult, inflammatory cells entering the eye are exposed to the pro-apoptotic agents transforming growth factor-b2 and Fas ligand. The expression of these molecules in the eye, and their action in killing inflammatory cells, has evolved as a means of preventing inflammation and subsequent loss of vision. Thus, the eye offers a unique and versatile system for studying the role of programmed cell death in lens development, vascular regression and immune privilege.

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Coincident loss of mitochondria and nuclei during lens fiber cell differentiation

Cited by 200 publications

References 18 publications

pRb and p107 regulate E2F activity during lens fiber cell differentiation

pRb and p107 regulate E2F activity during lens fiber cell differentiation

Caspase Remodeling of the Spectrin Membrane Skeleton during Lens Development and Aging

Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege

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