Next, Siekevitz and Palade became interested in membrane formation and found that various microsomal enzymes had different time courses of appearance in the endoplasmic reticulum. They demonstrated that there is a turnover of enzymes in the endoplasmic reticulum, with each protein having a characteristic half-life. From this, they inferred the presence of a substructure where newly synthesized enzymes were deposited.
Also, with Rachele Maggio, they carried out the first systematic fractionation of nuclei, leading to a clean separation of nucleoli and nucleoplasm that enabled a new era of biochemical investigation of the nucleus.
As an independent member of the Rockefeller faculty, Siekevitz changed the focus of his research to the nervous system and the events that occur at the neural synapse. By chance, he discovered postsynaptic density, a finding made a year earlier by Carl Cotman, and became convinced that the density represented a separate subcellular structure that underlies the postsynaptic membrane. For the next 16 years, Siekevitz and his colleagues incisively studied postsynaptic density, determining which proteins were attached to it. He retired from Rockefeller in 1988.
Siekevitz was elected to the National Academy of Sciences in 1975 and became the president of the American Society for Cell Biology in 1966 and president of the New York Academy of Sciences in 1976. He was an advocate of the social responsibilities of scientists and a founding member of the New York Scientists Committee for Public Information. He was also co-author of one of the first textbooks on cell biology, Cell Structure and Function, published in 1963.
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