Nuclear architecture in C. elegans

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

The nucleus is arguably one of the most important organelles in the cell, and yet surprisingly little is known about how its shape is maintained and what determines its size. The importance of nuclear shape is underscored by the fact that various diseases, including cancer and premature aging, are associated with changes in nuclear shape, and yet the relationship between nuclear shape and nuclear function is poorly understood. In most metazoan cells, the nuclear envelope (NE) undergoes cycles of assembly and disassembly in each and every cell cycle, and one of the key outstanding questions in the field is which proteins facilitate these processes. To gain insight into NE dynamics, we initiated the C. elegans nuclear architecture project. This project has three main components: (a) to examine in C. elegans the role of proteins identified in a yeast screen as being involved in nuclear architecture; (b) to screen for additional gene/proteins involved in determining nuclear shape and size, in affecting NE breakdown and reassembly, and in promoting pronuclear fusion after fertilization; and (c) to understand the function of the membrane reticulum, the centriculum, that surrounds the centrosome. Ultimately, are goal is to understand the mechanisms by which the nuclear envelope is remodeled during the cell cycle and during development. Following fertilization in C. elegans, the maternal and paternal chromosomes become encased in two distinct NEs, forming two pronuclei. These pronuclei migrate towards each other and become juxtaposed such that between them there are 4 closely apposed membranes (2 from each NE). During any mitosis, the NE disassembles and the nuclear membrane becomes highly fenestrated, but still surrounds the volume that is occupied but the chromosomes. We found that during the first embryonic mitosis, the permeabilization of the nuclear membrane between the two pronuclei requires the formation of membrane junctions that create membrane gaps through which parental chromosome mix. The formation of the gap is dependent on the C. elegans polo-like kinase, PLK-1, as well as other proteins. Additionally, we uncovered a membrane reticulum surrounding the centrosome, which we call the centriculum. We showed that the centriculum affect centrosome function, which is a novel concept as centrosomes were thought to be membraneless. We are currently testing the hypothesis that the centriculum serves as a microtubule filter, thereby ensuing high soluble tubulin concentration at the centrosome and limiting the number of microtubules that can extend to become astral microtubules.