Rethinking cell structure.

Abstract

Cell structure, emerging from behind the veil of conventional electron microscopy, appears far more complex than formerly realized. The standard plastic-embedded, ultrathin section can image only what is on the section surface and masks the elaborate networks of the cytoplasm and nucleus. Embedment-free electron microscopy gives clear, highcontrast micrographs of cell structure when combined with removal of obscuring material such as soluble proteins. The resinless ultrathin section is the technique of choice; it is simple and inexpensive, and it uses ordinary electron microscopes. The resulting pictures reveal a world of complex cell structure and function. These images necessarily change our conception of the cytoskeleton, nuclear matrix, mitosis, and the relation of membranes to cytostructure.The observational instruments of an experimental science often delineate its most fundamental ideas. In astronomy, every pivotal innovation in teloscopy literally recasts the cosmos: the simple Galilean telescope's discovery of Jupiter's moons was an unparalleled liberation from static, heliocentric heavens of crystalline spheres. Today, radio and y-ray telescopes give us an unsettled universe of neutron stars and black holes. In like manner, biology owes many of its basic concepts to a single class of instruments that reveal the invisible. The microscopes of Leuwenhoeck and Hooke first showed cells, and our notions of cell structure have evolved with improvements in light and electron optical instruments. Given the profound importance of microscopy to cell biology thought, it is quite surprising that the most powerful magnifying instrument of all, the transmission EM, affords a very truncated view of reality.Cell biology has long labored under a serious misperception of cell structure since conventional electron micrographs do not show most of the cell's architectural components. This is not an intrinsic technical weakness of electron imaging, however, and recent, very simple EM techniques give a far more accurate and detailed picture of cell structure. This review briefly explains the problem with conventional EM and how it is solved. Examples of the resulting EM images show that they differ profoundly from the customary picture of internal cell architecture.

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

“…A widely acknowledged mechanism for Golgi dispersal during microtubule disruption is that it results from random diffusion of Golgi elements no longer tethered together by microtubules . Recent biophysical studies on the properties of the cytoplasm, however, lead to the question of how random dispersal of membrane structures the size of Golgi fragments could occur throughout a cytoplasm consisting of a dense, gel-like cytoskeletal matrix (Luby-Phelps, 1994;Penman, 1995). Moreover, Golgi dispersal has been shown to be an energy-dependent and temperature-sensitive process (Turner and Tartakoff, 1989), indicating that microtubule depolymerization alone is not sufficient for Golgi dispersal.…”

Runx2 deficiency and defective subnuclear targeting bypass senescence to promote immortalization and tumorigenic potential

“…Tumors arise when cells override these intrinsic defenses. Cancer cells typically exhibit independence from extrinsic growth signals, lack of senescence or apoptosis, compromised telomeric integrity, and genomic instability, as well as changes in nuclear organization (2,(4)(5)(6). However, mice with genetic ablations of tumor suppressors are prone to tumorigenesis that is often lineage-restricted (7,8).…”

Role of Nuclear Matrix in Estrogen Regulated Gene Expression in Human Breast Cancer Cells

“…In recent years we have come to appreciate that functional components (e.g., transcript domains, RNA processing sites, sites of replication) of the nucleus are highly organized (Hendzel and Bazett-Jones, 1995;Penman, 1995;Xing et al, 1995). Transcribed genes are found in discrete foci Wansink et al, 1996).…”

“…The internal matrix of NM1-IF preparations has a fibrogranular appearance . Extraction of the NM1-IF with high salt removes proteins that decorate core filaments of the internal matrix (Penman, 1995;Nickerson et al, 1995).…”

“…The mechanical signalling pathway consists of the tissue matrix system that links together the three-dunensional skeletal networks, the extracellular matrix, cytoskeleton and nuclear matrix (Penman 1995; Maniotis et al 1997). The dynamic tissue matrix system governs cell and nuclear shape.…”