Golgi apparatus, cytological studies, metallic ions, Alfred A. Angrist, tissue sections, cytochemical, Albert Einstein College of Medicine, Cell Res, Alkaline phosphatase activity, cytoplasmic inclusions, Cancer Res, rat liver, endoplasmic reticulum
This Week's Citation Classic®
Novikofi A B & Goldfjscher S. Nucleosidediphosphatase activity in the Golgi
apparatus and its usefulness for cytological studies.
Proc. Nat. Acad. Sci. US 47:802-10, 1961.
[Department of Pathology
, Albert Einstein
College of Medicine. Bronx. NYI
The Colgi apparatus was visualized in animal and Plant Cell
s by an enzyme cytochemicat procedure free of the artifacts associated with the metallic methods of Cam lb Colgi. This was the first cytochemical demonstration of the Cobgi apparatus, an organelle that has received much attention from cell biologists. (The SCf~indicates that this paper has been cited in over 695 publications since 1961j Alex B. Novikoff Department of Pathology Albert Einstein College of Medicine Yeshiva University Bronx, NY 10461 July 23, 1985 My first papers in histochemistry were published while I was at the University of Vermont
where I was doing research in biochemistry. Three publications demonstrated that the staining of nuclei and salivary chromosome bands (after 1th3e Gomori-Takamatsu procedure) was an artifact. I studied the effects of different fixatives and metallic ions upon cytoplasmic particles isolated from rat liver homogenates and in tissue sections
, publishing the results in 1953.~Most biochemists at the time were of the opinion that enzymes could not be demonstrated cytochemically. But in fact, as we and others showed, the activities could be shown in situ, in tissues. In 1955, when I came to the Albert Einstein College of Medicine, I vigorously pursued this histochemical and cytochemical work. I was encouraged to do so by Alfred A. Angrist, the first chairman of thE Department
of Pathology. The enthusiasm and abilities of my assistants, Phyllis laciofano and Barbro Runling, were invaluable to my research. In 1958, Sidney Gotdfischer joined me as a research assistant
. To localize "nucleoside diphosphatase" in the cerebellum (the org5an used by Golgi with hi~classic metallic method ), we incubated sections for 3-18 hours, as opposed to the 60-90 minutes that we were using for liver and kid-
ney. We saw thata reaction product was deposited in a pattern suggesting the `Golgi apparatus." I was not sure whether the stained structures were extracellular or intracellular, and I telephoned Sanford Palay, at Harvard, for advice. He said he knewof nothing outside the cell resembling s~haIt described. I thought to myself, "If it is within the cell, it must be the Golgi apparatus!" In a wide variety of tissues, the enzyme cytochemical results were identical to those revealed by the capricious metal impregnation procedures. The ensuing paper was communicated to the Proceedings of the Nat iorta/ Academy of Sciences by Severo Ochoa. Our tests using other diphosphatase substrates in tissues with characteristic Golgi apparatus made it clear that there was a specific diphуsphatase (hydrolyzing UOP, IDP, GOP, and TPP) in the Golgi apparatus. These observations helped establish the very existence of the Golgi apparatus; its reality was th6e~subject of prolonged, often sharp controversy. Not only was the enzyme cyto. chemical method reproducible, it also provided the first information about the enzymatic properties of this ubiquitous and complex organelle. Combined staining for lysosomal acid phosphatase (j)-glycerophosphate or cytidine monophosphate as substrate) and Golgi nucleoside diphosphatase demonstrated a topographical and, presumably, a functional association between the Golgi аpparatus and lysosomes. Subsequent studies revealed that lysosomes probably originated from a region of smoothendoplasmic reticulum situated at the trans aspect o9f the Golgi apparatus. This region I termed GERL. The role of GERL in processing lysosomal enzymes is currently under investigation in my laboratory. We utilized nucleoside diphosphatase to distinguish the trans aspectof the Golgi apparatu1s0(Daniel Friend made me aware of this distinction )and the endoplasmic reticulum, in some cells; NADHtetrazolium reductase to visualize the mitochondna; catalase to localize the peroxisomes and microperoxisomes; and aci1d1 1p2hosphatase to reveal the lysosomes and GERL. ' We are currently using immunocytochemistry to visualize other enzymes in the Golgi apparatus and in lysosomes. The development of the GERL concept evolved slowly from the earlier studies on the Golgi apparatus. We view this organelle as part of a unique cellular processing system.
1. Penrnon B. Novlkoft A B & Morrlan. 1G. The histochemical localization of alkaline ptiosphatase during csrcinogenesis in rats ted p-dimethylaminoazobenzene. Cancer Res
. 10:557-64. 1950. 2. Novlkqff A B. Histochernical demonstration of nuclearenzymes. Exp. Cell Res. (Suppb. 21:123-43. 1952. 3. Novlkoff A B. Korson L & Spnter H W. alkaline phosphatase
activity in the Golgi substance of intestinal mucosa. Erp. Cell Res. 3:617-IS. 1952. 4. Novlkotf A B, Podher E, Ry.n I & Noc E. Biochemical heterogeneity of the cytoplasmic particles isolated from rat liver homogenate. I. Hi.stochem. Cssochem. 1:27-46. 1953. (Cited 165 times since 1955.) 5. Golglt. Sur Ia structure des cetlutes nerveuses. Arch. hal. Biol. 30:60-73. 189t. (Cited 60 times since 1955.) 6. Galeahv I 0, Mousu I A A & Dosekun F. The cytoplasmic inclusions of the fixed spinal cord cells of the kitten with the Zernicke microscope and Sudan dyes. Cellale 53:13-32. 1949. 7. Baker 1 R. New developments in the Golgi controversy.). Roy. Microsc. Soc. 82:145-57. 1963. 8. Palad. G Ј & Chad. A. The nature of the Golgi apparatus. 1. Parallelism between intercellular myeLin Figure
i and Golgi apparatus in somatic cells.). Morphology 85:35-112, 1949. 9. Noelkoft A B. GERL. its form and function in neurons of rat spinal ganglia. 8th!. Bid!. 127:358. 3964. (Cited 325 times.) Ill. Cbeeeham RD. Morr~DI. Pannek C & Friend D S. Isolation ot a Golgi apparatus-rich traction from rat liver. IV. Thiamine pyrophosphatase.f. Cell Biol. 49:899-905. 1971. (Cited 60 times.) II. Nos4kolf A B. The endoplasmic reticulum: a cytochemist's view a review). Proc. Nat. Acad. Sd. US 73:2781-7. 1976. (Cited 315 timex. 12. Nowlkoff A B & Novikoft P M. Cytochemical contributions to differentiating GERL from the Golgi apparatus.: Hаtockemicall. 9:525-51. 1977. (Cited 375 times.)
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