There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

/pdf/inositol-trisphosphate-and-diacylglycerol-as-second-4drzjsg27y.pdf

Inositol trisphosphate and diacylglycerol as second messengers.

https://www.cell.com/cell/pdf/0092-8674(87)90585-X.pdf

Expression of a single transfected cDNA converts fibroblasts to myoblasts.

https://www.cell.com/molecular-cell/pdf/S1097-2765(00)80057-X.pdf

Positionally Cloned Gene for a Novel Glomerular Protein—Nephrin—Is Mutated in Congenital Nephrotic Syndrome

Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumors by administration of glucose (+/- insulin) and by drugs such as hydralazine which modify the relative blood flow to tumors and normal tissues. Cells have evolved mechanisms for regulating their intracellular pH. The amiloride-sensitive Na+/H+ antiport and the DIDS-sensitive Na+-dependent HCO3-/Cl- exchanger appear to be the major mechanisms for regulating pHi under conditions of acid loading, although additional mechanisms may contribute to acid extrusion. Mitogen-induced initiation of proliferation in some cells is preceded by cytoplasmic alkalinization, usually triggered by stimulation of Na+/H+ exchange; proliferation of other cells can be induced without prior alkalinization. Mutant cells which lack Na+/H+ exchange activity have reduced or absent ability to generate solid tumors; a plausible explanation is the failure of such mutant cells to withstand acidic conditions that are generated during tumor growth. Studies in tissue culture have demonstrated that the combination of hypoxia and acid pHe is toxic to mammalian cells, whereas short exposures to either factor alone are not very toxic. This interaction may contribute to cell death and necrosis in solid tumors. Acidic pH may influence the outcome of tumor therapy. There are rather small effects of pHe on the response of cells to ionizing radiation but acute exposure to acid pHe causes a marked increase in response to hyperthermia; this effect is decreased in cells that are adapted to low pHe. Acidity may have varying effects on the response of cells to conventional anticancer drugs. Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi. It is suggested that acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.

/pdf/acid-ph-in-tumors-and-its-potential-for-therapeutic-3pjbj72nxi.pdf

Acid pH in Tumors and Its Potential for Therapeutic Exploitation

PERSPECTIVES AND SUMMARY 70 CHEMISTRY OF ACYL LINKAGES TO PROTEINS 71 BIOLOGY OF N-MYRISTOYLATION 73 Myristoylation of p60v-src. . . . . . . . . . . . . . . . . . . . . . .. . . . . . •. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . •. •. . . . . . . 74 M yristoylation Q{ Retrovirus Structura l Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 N-Myristoylated Protein s Have Diff erent Intracellular Destinations. . . . . . . . . . . . . . . . . . . . 76 Regu lation o f Protein M yristoylation in Response to Hormonal Signa ls . . . . . . . . . . . . . . 78 MYRISTOYL COA: PROTEIN N-MYRISTOYL TRANSFERASE 78 An A ssay for NMT. . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 79 Fatty Acid Sp ec ificity of NMT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ 79 Yeast NMT P eptide Substrate Spec ificity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Importance of Sequ ence Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 86 NMT in High er Eu karyotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 87 Identification of P otential N-Myristoylproteins from cDNA Data Bases . . . . . . . . . . . . . . . 88 ESTER-LINKED ACYLATION OF CELLULAR PROTEINS 88 M ye lin P roteolipid Proteins. . . . . . . . . . . . . . . . . . 90 Viral Glycoproteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Tran sferrin Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . .. . . . . . . . . 92 Mucus Glycoprotein s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 The RAS Family of G Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . .. . . . . . . . . . . . . . . . . 93 FUTURE DIRECTIONS 94

The biology and enzymology of eukaryotic protein acylation

The Effect of Carbon and Nitrogen Sources on the Level of Metabolic Intermediates in Escherichia coli

In the preceding paper (Salzer et al., 1980, J. Cell Biol. 84:753--766), evidence was presented that a neurite membrane fraction could be used to stimulate Schwann cell proliferation in culture. In this study, we present evidence that the mitogenic signal by which intact neurites or neurite membranes stimulate Schwann cell proliferation is located at the neurite surface. This conclusion is based on the following observations: (a) stimulation of Schwann cell proliferation by neurons requires direct contact between neurites and Schwann cells, separation of the two cells by a permeable collagen diaphragm 6 microns thick prevents Schwann cell proliferation; (b) treatment of intact neurites with trypsin before preparation of neurite membranes abolishes the ability of these membranes to be mitogenic for Schwann cells; and (c) the mitogenic activity of neurite homogenates is exclusively localized in the particulate rather than the soluble fraction of the homogenate. The mitogenic component on the neurite surface is heat labile, and is inactivated by aldehyde fixation. Preliminary data suggest that the mitogenic effect of neurite on Schwann cells is not mediated by 3',5'-cyclic AMP.

/pdf/studies-of-schwann-cell-proliferation-iii-evidence-for-the-1mpo7og78j.pdf

Studies of Schwann cell proliferation. III. Evidence for the surface localization of the neurite mitogen.

Cell–cell interactions are of critical importance during neural development, particularly since the migration of neural cells and the establishment of functional interactions between growing axons and their target cells1,2 has been suggested to depend upon cell recognition processes Neurone–neurone adhesion has been well studied in vitro, and is mediated in part by the neural cell adhesion molecule N-CAM3–7 N-CAM-mediated cell–cell adhesion has been postulated to occur by a homophilic binding mechanism8, in which N-CAM on the surface of one cell binds to N-CAM on a neighbouring cell Studies in our laboratory have identified a cell surface glycoprotein, now known to be N-CAM9, which participates in cell–substratum interactions in the developing chicken nervous system10–12 Although this adhesion involves a homophilic binding mechanism, the binding of the cell surface proteoglycan heparan sulphate to the glycoprotein is also required13 This raises the question of whether the binding of heparan sulphate to N-CAM is also required for cell-cell adhesion Here we show that the binding of retinal probe cells to retinal cell monolayers is inhibited by heparin, a functional analogue of heparan sulphate, but not by chondroitin sulphate Monoclonal antibodies that recognize two different domains on N-CAM, the homophilic-binding and heparin-binding domains, inhibit cell–cell adhesion The heparin-binding domain isolated from N-CAM by selective proteolysis also inhibits cell-cell adhesion when bound to the probe cells

Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules.

When prepared by methods utilized in our laboratory, pure populations of Schwann cells in culture do not divide, but, after recombination with peripheral sensory neurons or their processes, proliferate rapidly (Wood and Bunge, 1975, Nature (Lond.) 256:661--664). In this paper, we demonstrate that a membrane fraction prepared from sensory ganglion neurites is also mitogenic for Schwann cells and increases the labeling index (assessed by autoradiography after incubation of cells with tritiated thymidine) from less than 0.2 to 10% for primary cells, and from 0.4 to 18--19% for replated cells. The increased responsiveness of replated cells may reflect their greater access to the neurite membranes which is a consequence of the elimination of multiple cell layers after replating and the removal of the basal lamina. This stimulation was specific; addition of membrane preparations from other cell types (3T3, C1300, etc.) was not mitogenic. Ultrastructural analysis demonstrated apparent binding of neurite membranes to Schwann cells as well as significant phagocytosis of the membranes by the cells. The uptake of nonmitogenic membranes suggests that phagocytosis per se is not the stimulus of proliferation.

https://rupress.org/jcb/article-pdf/84/3/753/1401048/753.pdf

Luis Glaser

Papers

The biology and enzymology of eukaryotic protein acylation

The Effect of Carbon and Nitrogen Sources on the Level of Metabolic Intermediates in Escherichia coli

Studies of Schwann cell proliferation. III. Evidence for the surface localization of the neurite mitogen.

Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules.

Studies of Schwann cell proliferation. II. Characterization of the stimulation and specificity of the response to a neurite membrane fraction.