Abstract. The fiber cells of the eye lens possess a unique cytoskeletal system known as the "beadedchain filaments" (BFs). BFs consist of filensin and phakinin, two recently characterized intermediate filament (IF) proteins. To examine the organization and the assembly of these heteropolymeric IFs, we have performed a series of in vitro polymerization studies and transfection experiments. Filaments assembled from purified filensin and phakinin exhibit the characteristic 19-21-nm periodicity seen in many types of IFs upon low angle rotary shadowing. However, quantitative mass-per-length (MPL) measurements indicate that filensin/phakinin filaments comprise two distinct and dissociable components: a core filament and a peripheral filament moiety. Consistent with a nonuniform organization, visualization of unfixed and unstained specimens by scanning transmission electron microscopy (STEM) reveals the existence of a central filament which is decorated by regularly spaced 12-15-nm-diam beads. Our data suggest that the filamentous core is composed of phakinin, which exhibits a tendency to self-assemble into filament bundles, whereas the beads contain filensin/phakinin hetero-oligomers. Filensin and phakinin copolymerize and form filamentous structures when expressed transiently in cultured cells. Experiments in IF-free SWl3 cells reveal that coassembly of the lens-specific proteins in vivo does not require a preexisting IF system. In epithelial MCF-7 cells de novo forming filaments appear to grow from distinct foci and organize as thick, fibrous laminae which line the plasma membrane and the nuclear envelope. However, filament assembly in CHO and SV40-transformed lensepithelial cells (both of which are fibroblast-like) yields radial networks which codistribute with the endogenous vimentin IFs. These observations document that the filaments formed by lens-specific IF proteins are structurally distinct from ordinary cytoplasmic IFs. Furthermore, the results suggest that the spatial arrangement of filensin/phakinin filaments in vivo is subject to regulation by host-specific factors. These factors may involve cytoskeletal networks (e.g., vimentin IFs) and/ or specific sites associated with the cellular membranes.
Sequence attributes predict that the ABP subunits expressed in lacrimal glands comprise proteins that are secreted in tears. These data imply compositional differences in ABPs secreted by mouse lacrimal and submandibular glands, and in ABPs secreted by male and female mouse lacrimal glands.
In this paper, we consider the ocular lens in the context of contemporary developments in biological ideas. We attempt to reconcile lens biology with stem cell concepts and a dearth of lens tumors.Historically, the lens has been viewed as a closed system, in which cells at the periphery of the lens epithelium differentiate into fiber cells. Theoretical considerations led us to question whether the intracapsular lens is indeed self-contained. Since stem cells generate tumors and the lens does not naturally develop tumors, we reasoned that lens stem cells may not be present within the capsule. We hypothesize that lens stem cells reside outside the lens capsule, in the nearby ciliary body. Our ideas challenge the existing lens biology paradigm.We begin our discussion with lens background information, in order to describe our lens stem cell hypothesis in the context of published data. Then we present the ciliary body as a possible source for lens stem cells, and conclude by comparing the ocular lens with the corneal epithelium.
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