Glc7p is the catalytic subunit of type 1 protein phosphatase (PP1) (5), which is a member of the highly conserved PPP family of protein serine-threonine phosphatases (11). Like mammalian PP1 catalytic subunits, Glc7p regulates many physiological processes, including glycogen metabolism, glucose repression, transcription, membrane fusion, sporulation, mitosis, ion homeostasis, and cell wall organization (12, 13, 14). Glc7p functions in opposition to the Ipl1p Aurora kinase to ensure proper levels of histone H3 phosphorylation and the fidelity of chromosome segregation during mitosis (15). Glc7p also appears to function in opposition to the Gcn2p kinase in modulating phosphorylation levels of the Sui2p alpha-subunit of translation initiation factor eIF2, which effects translation of some mRNAs (16). Glc7p dephosphorylates proteins involved in a variety of processes including Cbf2p (an essential kinetochore protein) (17), Fin1p (mitosis) (18), and Red1p (meiotic chromosome segregation) (19). Scd5p, which is involved in cortical actin organization and endocytosis, and Npl3p, which is involved in mRNA export, are both activated by Glc7p-dependent dephosphorylation (20, 21, 22).

Glc7p itself has little substrate specificity (23). Instead, specificity is dictated by regulatory subunits that target Glc7p to various substrates for different functions under different growth conditions (24), or alter its activity (6). Glc7p is targeted to the bud neck before bud emergence by Bni4p, which is required for the assembly of the chitin ring, and is also involved in septum formation and the maintenance of bud neck integrity (25, 26). Glc7p is targeted to the bud cortex and shmoo tip by Bud14p, and Bud14p-Glc7p interactions are important for bud-site selection, filamentous growth, polarized growth, and transcription of some STRE-dependent genes (27, 28). Gac1p targets Glc7p to the glycogen synthase Gsy2p, is required for glycogen accumulation, and is involved in the transcription of some heat-shock responsive genes (14, 29). Reg1p is required for the involvement of Glc7p in various processes including glucose repression, cell growth, and glycogen accumulation (24), and Sip5p may increase Glc7p-Reg1p complex binding to Snf1p (30). Reg2p appears to target Glc7p to substrates that are phosphorylated by Snf1p during glucose repression (31). Ref2p targets Glc7p to the cleavage and polyadenylation factor-containing complex (holo-CPF), that associates with the 3' ends of mRNA-encoding genes and also with snoRNA genes, and is involved in pre-mRNA polyadenylation and snoRNA 3'-end maturation (32).

Although GLC7 is induced during stationary phase, the level of GLC7 mRNA is constant during exponential growth (5). Glc7p displays a constant level of activity throughout the cell cycle, and is quite stable, with a half-life of several generations (180 minutes) (6). Glc7p activation by the regulatory subunit Glc8p is important for stationary phase and chromosome segregation, and to a lesser degree for glycogen accumulation (6, 33, 34). Glc7p is also activated by the PP1 regulator Shp1p, either directly or indirectly, which effects sporulation and normal growth (35, 24), and is inhibited by the PP1 inhibitor Ypi1p (36).

Glc7p is found in a variety of cellular locations, as dictated by its various functions and targeting partners, including spindle pole bodies from start of anaphase until cytokinesis, the bud neck ring after anaphase, the base of mating projections in alpha-factor treated cells, and in the nucleus with high concentrations in the nucleolus throughout the mitotic cell cycle (37). Glc7p requires Sds22p for its for normal nuclear localization during mitosis (38, 13), and requires Gip1p for its meiotic nuclear localization and involvement in the regulation of septin organization and spore wall formation (39).

While glc7 null mutants are inviable, reduction-of-function mutations result in a wide range of phenotypes. glc7-1 mutants display a severe defect in glycogen accumulation but normal glucose repression, whereas glc7-T152K mutations do not prevent glycogen accumulation, but do relieve glucose repression (40). At restrictive temperatures, glc7-10 mutants display a high frequency of chromosome loss, hyperphosphorylation of Cbf2p (17), a high proportion of budded cells with an unmigrated nucleus, duplicated spindle pole bodies, a short spindle, delocalized cortical actin and 2C DNA content (41). glc7-109 mutants display a dominant hyperglycogen defect and recessive ion and drug sensitivity (14). glc7-129, glc7-131, and glc7-127 mutants display elevated levels of mitotic histone H3 phosphorylation (42), and glc7-129 cells also display a G2/M cell cycle arrest (43). glc7Y-170 mutants display a defect in the G2/M phase of the cell cycle (44). GLC7 mutations have also been associated with defects in premeiotic DNA synthesis and sporulation (34) and depletion of Glc7p is associated with G1 arrest (34). Overexpression of GLC7 results in chromosome missegregation (15, 35), growth defects, aberrant bud morphology (45), and mitotic delay with increased numbers of large budded cells which are blocked in mitosis (45).

Amino acid sequences of catalytic subunits of type 1 protein phosphatase are highly conserved across many species (34), such that GLC7 displays similarity to many PP1 eukaryotic counterparts, including Schizosaccharomyces pombe dis2, Drosophila melanogaster and rabbit protein phosphatase 1 catalytic subunits (5), and human PPP1CA and PPP1CB, PPP1CC (10, 12).

Last updated: 2005-11-01