Cellular distribution

Fritschy J-M, Mohler H (1995) GABAA-receptor heterogeneity in the adult rat brain differential regional and cellular distribution of seven major subunits. J Comp Neurol 14 154-94... 

Penninks Seinen (1980) looked at subcellular distribution of dibutyltin in rat liver and thymus cells in vitro. Radioactivity was concentrated in mitochondria and low in cytoplasm in thymus cells, in marked contrast to liver cells, where mitochondrial radioactivity was very low. Differences in cellular distribution have been suggested as a reason for the selective effect on the thymus. 

A variety of different methodologies has been employed to investigate the neurotransmitter systems involved in control of behavioral states. Biochemical experiments have elucidated the pathways and enzymes involved in the synthesis, degradation, release and reuptake of different neurotransmitters. Immuno-histochemical techniques have allowed the visualization of their cellular and sub-cellular distribution throughout the nervous system as well as the distribution of their receptors and uptake systems. Chemical sampling techniques, including... 

The IFN-y receptor (the type II receptor) displays a more limited cellular distribution than that of the type I receptors (Table 8.5). This receptor is a transmembrane glycoprotein of molecular mass 50 kDa, which appears to function as a homodimer. The extracellular IFN-y binding region consists of approximately 200 amino acid residues folded into two homologous domains. Initiation of signal transduction also requires the presence of a second transmembrane glycoprotein known as AF-1 (accessory factor 1), which associates with the extracellular region of the receptor. 

The nervous system contains an unusually diverse set of intermediate filaments (Table 8-2) with distinctive cellular distributions and developmental expression [21, 22]. Despite their molecular heterogeneity, all intermediate filaments appear as solid, rope-like fibers 8-12 nm in diameter. Neuronal intermediate filaments (NFs) can be hundreds of micrometers long and have characteristic sidearm projections, while filaments in glia or other nonneuronal cells are shorter and lack sidearms (Fig. 8-2). The existence of NFs was established long before much was known about their biochemistry or properties. As stable cytoskeletal structures, NFs were noted in early electron micrographs, and many traditional histological procedures that visualize neurons are based on a specific interaction of metal stains with NFs. 

Moore, D., Chambers, J., Waldvogel, H., Faull, R. and Emson, P. Regional and cellular distribution of the P2Y, purinergic receptor in the human brain striking neuronal localisation. J. Comp. Neurol. 421 374-384, 2000. 

There are multiple isoforms of the a and p subunits of soluble GC that exhibit distinct tissue and cellular distributions. Most of the isoforms are expressed in brain, including 0Ci 3 and and P3. The p2 subunit is found primarily in lung. This isoform also contains a consensus sequence at its carboxy terminus for isoprenylation or carboxymethyl-ation, which could serve to anchor the protein to the plasma membrane. It has been proposed that specific isoforms of the a and P subunits of GC may form heterodimers with distinct functional and regulatory properties, although this remains to be established with certainty. 

Protein kinase C (PKC) comprises the other major class of Ca2+-dependent protein kinases and is activated by Ca2+ in conjunction with DAG and phosphatidylserine (discussed in Ch. 20). Multiple forms of PKC have been cloned, and the brain is known to contain at least seven species of the enzyme. The variant forms of PKC exhibit different cellular distributions in the brain and different regulatory properties. For example, they differ in the relative ability of Ca2+ and DAG to activate them some require both Ca2+ and DAG, whereas others can be activated by DAG alone, apparently without an increase in cellular Ca2+ concentrations. However, these enzymes show similar substrate specificities and, as a result, are often considered isoforms. 

Redo, A., J.A. Marigomez, E. Angulo, and J. Moya. 1988a. Zinc treatment of the digestive gland of the slug Arion ater L. 1. Cellular distribution of zinc and calcium. Bull. Environ. Contam. Toxicol. 41 858-864. 

Mitchner NA, Garlick C, Ben-Jonathan N (1998) Cellular distribution and gene regulation of estrogen receptors a and f) in the rat pituitary gland. Endocrinology 139 976-3983... 

Costa, M., Simmons-Hansen, J., Bedrossian, C. W. M., Bonura, J. and Caprioli, R. M. (1981). Phagocytosis, cellular distribution, and carcinogenic activity of particulate nickel compounds in tissue culture, Cancer Res., 41, 2868-2876. 

The cellular uptake appears to be a passive process, the cellular distribution being dependent on cell type. In cultured pneumocytes, the cell membrane was... 

In mammals there are four genes for the PMCA pump, two of which are expressed in all tissues (housekeeping enzymes), whereas the other two, which have a particularly high affinity for calmodulin, are restricted in their cellular distribution, notably to neurons. Additional variants of PMCAs are produced by alternative splicing of their primary RNA transcripts. 

Antibodies are powerful tools in pharmaceutical development, and as den-drimers are incorporated into various drugs and medical devices, antibodies such as described should be useful to study dendrimer biodistribution and pharmacokinetic properties. We have not attempted to detect PAMAM de-ndrimers in biological fluids (blood, urine, sputum, etc.), but expect that it would work. Additionally, the antibodies might be used in immunohistochemistry to study the tissue and cellular distribution of dendrimer therapeutics. 

Interestingly, the cellular distribution was analyzed by energy-filtered transmission electron microscopy and electron tomography, demonstrating the presence of free fullerene in the cytoplasm, or associated with nuclear membrane, plasma membrane, lysosomes and, rather surprisingly, with the nucleus (Porter et al., 2006, 2007). 

Joshi M, Tyndale RF. 2006. Regional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine. Neuropharmacology 50 568-575. 

Miksys S, Rao Y, Sellers EM, Kwan M, Mendis D, et al. 2000. Regional and cellular distribution of CYP2D subfamily members in rat brain. Xenobiotica 30 547-564. 

The cellular distribution of 26S proteasome subunits in yeast appears to be similar as in higher eukaryotes but there also exist some differences in the details. Indirect immunoflourescence studies localized the GFP-tagged yeast 26 proteasome primarily to the yeast nucleus and the nuclear periph-... 

Rosania, G.R. (2003) Supertargeted chemistry identifying relationships between molecular structures and their sub-cellular distribution. Current Topics in Medicinal Chemistry, 3 (6), 659-685. 

Viola, G., Facciolo, L., Dall Acqua, S., Di Lisa, F., Canton, M., Vedaldi, D., Fravolini, A., Tabarrini, O. et al. (2004) 6-Aminoquinolones photostability, cellular distribution and phototoxicity. Toxicology In Vitro An International Journal Published in Association with BIBRA, 18, 581-592. 

---