J. Cell Biol., Volume 141, Number 5, June 1, 1998 1207-1215

Differential Subcellular Localization of Protein Phosphatase-1 , 1, and  Isoforms during Both Interphase and Mitosis in Mammalian Cells

Paul R. Andreassen,^* Françoise B. Lacroix,^* Emma Villa-Moruzzi, and Robert L. Margolis^*

^* Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS), 38027 Grenoble cedex 1, France; and  Department of Biomedicine, University of Pisa, 56126 Pisa, Italy

Protein phosphatase-1 (PP-1) is involved in the regulation of numerous metabolic processes in mammalian cells. The major isoforms of PP-1, , 1, and , have nearly identical catalytic domains, but they vary in sequence at their extreme NH₂ and COOH termini. With specific antibodies raised against the unique COOH-terminal sequence of each isoform, we find that the three PP-1 isoforms are each expressed in all mammalian cells tested, but that they localize within these cells in a strikingly distinct and characteristic manner. Each isoform is present both within the cytoplasm and in the nucleus during interphase. Within the nucleus, PP-1  associates with the nuclear matrix, PP-1 1 concentrates in nucleoli in association with RNA, and PP-1  localizes to nonnucleolar whole chromatin. During mitosis, PP-1  is localized to the centrosome, PP-1 1 is associated with microtubules of the mitotic spindle, and PP-1  strongly associates with chromosomes. We conclude that PP-1 isoforms are targeted to strikingly distinct and independent sites in the cell, permitting unique and independent roles for each of the isoforms in regulating discrete cellular processes.

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