How proliferating cells maintain the copy number and overall size of their organelles is not clear. In the budding yeast Saccharomyces cerevisiae the G1 cyclins Cln1,2,3p control initiation of cell division by regulating the activity of the cyclin-dependent kinase (Cdk) Cdc28p. We show that Cln3p controls vacuolar (lysosomal) biogenesis and segregation. First, loss of Cln3p, but not Cln1p or Cln2p, resulted in vacuolar fragmentation. Although the vacuoles of cln3Δ cells were fragmented, together they occupied a large space, which accounted for a significant fraction of the overall cell size increase in cln3Δ cells. Second, cytosol prepared from cells lacking Cln3p had reduced vacuolar homotypic fusion activity in cell-free assays. Third, vacuolar segregation was perturbed in cln3Δ cells. Our findings reveal a novel role for a eukaryotic G1 cyclin in cytoplasmic organelle biogenesis and segregation. Furthermore we show that the scaffold protein Bem1p, a critical regulator of Cdc42p activity, is a downstream effector of Cln3p/Cdc28p complex. The Cdc42p GTPase is known to be required for vacuole fusion. Our results suggest that Ser72 on Bem1p is phosphorylated by Cdc28p in a Cln3p-dependent manner to promote vacuole fusion. Replacing Ser72 with Asp, to mimic phosphorylation at an optimal Cdkconsensus site located in the first SH3 domain of Bem1p, suppressed vacuolar fragmentation in cells lacking Cln3p. Using in vivo and in vitro assays, we found that Cln3p was unable to promote vacuole fusion in the absence of Bem1p or in the presence of a non-phosphorylatable Bem1p-Ser72Ala mutant. Furthermore, activation of Cdc42p also suppressed vacuolar fragmentation in the absence of Cln3p. Our results provide a mechanism that links cyclin-dependent kinase activity with vacuole fusion through Bem1p and the Cdc42p GTPase cycle.

Diss.--Augsburg. / Bibliogr. p. 210-222.

Thesis (M.S.)--University of North Texas, May, 2009. / Title from title page display. Includes bibliographical references.

Thesis (M.S.), Eastern Illinois University, 2003. / Includes bibliographical references (leaves 44-48).

Thesis (Ph. D.)--University of Notre Dame, 2003. / Thesis directed by Jeanne D. Day for the Department of Psychology. "December 2003." Includes bibliographical references (leaves 98-106).

Thesis (Ed. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xi, 156 p. Vita. Includes abstract. Includes bibliographical references (p. 130-139).

Early childhood—a period of development that research has established as a critical period for establishing a foundation to support later development and well-being—is increasingly likely to take place in multiple contexts. Continuity and discontinuity in children’s exposure to environmental chaos across two important contexts for their early development: (1) the home and (2) the early learning and care (ELC) setting were examined using data from a large representative sample of low-income preschool children attending Head Start in order to determine how children’s exposure to chaos in each context combine to either promote or interfere with their social-emotional and cognitive development over a year of preschool. A series of multi-level models tested whether children’s experiences of chaos, operationalized in three ways: (1) as individual indicators of crowding, lack of routines, and instability in each setting; (2) as a cumulative index of chaos in each setting; and (3) as a profile that incorporated children’s experiences across setting, influenced children’s social-emotional and cognitive development. Both household and classroom chaos predicted children’s development, but children’s experiences in their home environments were the predominant influence, indicating that children who had non-chaotic home environments gained more over the preschool year than did children who had chaotic homes. These findings provide additional support that effective and high-quality early education and care settings must incorporate children’s home and family experiences. / text

Not available / text

Not available / text

No description available.