Nucleomorphin: a nucleolar calmodulin binding protein that regulates nuclear number

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The nucleolus is a special compartment in the cell nucleus that is a central controlling element in cell division of normal and cancer cells. Originally considered simply a ribosome factory it now is known to have many other critical functions. It is involved in the cell cycle, life span, viral replication, molecular sequestering, and stress responses, among other activities. We have discovered and have studied a nucleolar protein called nucleomorphin (NumA1) in Dictyostelium discoideum. Dictyostelium is recognized as a model organism for the study of cell and developmental biology. NumA1 now represents the most well studied nucleolar protein in Dictyostelium. Like nucleolar proteins in humans, NumA1 has nucleolar and nuclear localization signals plus an extensive stretch of acidic amino acids (glutamic acid/aspartic acid). When this acidic amino acid sequence is removed, the cells become highly multinucleated. Cells typically have a single nucleus suggesting NumA1 is involved in the regulation of nuclear number. NumA1 binds to calcium binding protein (CBP4a) in a calcium-dependent manner via this acidic stretch of acids suggesting it too is involved in NumA1 function. We will knockout the gene for CBP4a to learn what its role is in regulating nuclear number and in other cell functions. In other species, nucleolar proteins move back and forth between the nucleolus, nucleoplasm and cytoplasm but exactly how this is controlled remains elusive. We will study the phosphorylation of NumA1 as well as its nucleolar and nuclear localization signals to determine if this is what controls this translocation. Along with related experiments, this work will provide major advances into the roles of two nucleolar proteins in cell function and in how nuclear number is regulated. In the long term, we believe it will set the stage for using Dictyostelium as a model system for the study of nucleolar structure and function in all organisms.